Compositions and methods for treating myelodysplastic syndrome with glycine transport inhibitors

Abstract

The present embodiments are directed to methods of using glycine transporter inhibitors, such as GlyT1 inhibitors, or pharmaceutically acceptable salts, solvates or prodrugs thereof, or pharmaceutical compositions thereof, for preventing or treating MDS, and related syndromes / conditions / symptoms thereof.

Description

[0001] COMPOSITIONS AND METHODS FOR TREATING MYELODYSPLASTIC SYNDROME WITH GLYCINE TRANSPORT INHIBITORS RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No.63 / 697,765, filed September 23, 2024, which application is hereby incorporated by reference in its entirety. FIELD OF THE DISCLOSURE Embodiments disclosed herein are directed to methods and uses to prevent or treat myelodysplastic syndrome (MDS), or one or more complications or symptoms of MDS, with one or more glycine transporter inhibitors, such as, but not limited to, GlyT1 inhibitors, or pharmaceuticaly acceptable salts, solvates, prodrugs thereof, or pharmaceutical compositions thereof. BACKGROUND OF THE DISCLOSURE The myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cels in the bone marow do not mature of become healthy blood cels. These myeloid malignancies arise from bone marrow (BM) hematopoietic stem cels (HSCs). There are over 50 recurent somatic mutations that have been identified in MDS, with over 90% of patients carrying at least one clonal somatic mutation. The diferent types of MDS are characterized by ineffective hematopoiesis, which results in peripheral blood cytopenia. Refractory anemia results from too few red blood cels (RBCs) in the blood, with a normal level of both white blood cels and platelets. Refractory anemia with ring sideroblasts occurs when there are too few RBCs in the blood and the RBCs have too much iron inside the cel; similar to refractory anemia, there is a normal level of both white blood cels and platelets. A patient having too few RBCs in the blood having 5-19% blasts in the bone marow is characterized as having refractory anemia with excess blasts. This patient may also display changes to the white blood cels and platelets and may progress to acute myeloid leukemia (AML). Refractory cytopenia with multilineage dysplasia results from too few of at least two types of blood cels (red blood cels, platelets, or white blood cels). Additionaly, less than 5% of the cels in the bone marow are blasts and less than 1% of the cels in the blood are blasts. In some instances, afected RBCs may have extra iron. Refractory cytopenia may also progress to acute myeloid leukemia (AML). When there are too few of one type of blood cel (red blood cels, platelets, or white blood cels), a patient is said to have refractory cytopenia with unilineage dysplasia. Additional characteristics are changes in 10% or more of two other types of blood cels, less than 5% of the cels in the bone marow are blasts, and less than 1% of the cels in the blood are blasts. Unclassifiable MDS arises when the numbers of blasts in the bone marow and blood are normal, and the disease is not one of the other myelodysplastic syndromes. Finaly, MDS associated with an isolated del(5q) chromosome abnormality occurs when there are too few RBCs in the blood, less than 5% of the cels in the bone marrow and blood are blasts, and there is a specific change in the chromosome. For the majority of patients with lower-risk myelodysplastic syndrome (LR-MDS), one of the primary clinical goals is to aleviate the symptoms associated with the resultant cytopenia and to minimize the transfusion burden. While supportive red blood cel (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, frequent transfusions are often complicated by iron overload and decreased quality of life; furthermore, most patients either do not respond to ESAs or wil eventualy develop resistance. As such, there is a great need for further therapeutic options in the management of anemia related to MDS. Moreover, there is a need for new methods and compositions for treating MDS and / or treating one or more complications associated with LR-MDS, such as cytopenia including anemia. SUMMARY OF THE DISCLOSURE In certain aspects, the disclosure provides for a method of treating a myelodysplastic syndrome (MDS) in a subject, the method comprising administering to the subject a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt. In certain embodiments, the treating is with the proviso the MDS is not MDS with isolated del(5q) chromosome. In certain aspects, the disclosure provides for a method of treating one or more symptoms or complications of a myelodysplastic syndrome (MDS) in a subject, the method comprising administering to the subject a pharmaceutical composition comprising one or more GlyT1 inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its pharmaceuticaly acceptable salt. In some embodiments, the one or more symptoms or complications of MDS is selected from the group consisting of: edema, erythema, anemia, hypochromic anemia, hemolytic anemia, hemolysis, mild hemolysis, severe hemolysis, chronic hemolysis, inefective erythropoiesis, hemochromatosis, hemosiderosis, petechiae, difficulty breathing, recuring infections, hemorhage, thrombocytopenia, and acute myeloid leukemia (AML). In some embodiments, the MDS is selected from the group consisting of i) MDS with multilineage dysplasia (MDS-MLD), i) MDS with single lineage dysplasia (MDS-SLD), ii) MDS with ring sideroblasts (MDS-RS), iv) MDS with excess blasts (MDS-EB), and v) unclassifiable MDS. In some embodiments, the subject is classified based on the World Health Organization Prognostic Scoring system (WPSS) as very low, low or intermediate. In some embodiments, the MDS is selected from the group consisting of i) MDS with multilineage dysplasia (MDS-MLD), and i) MDS with single lineage dysplasia (MDS-SLD). In some embodiments, the subject is classified as lower-risk MDS (LR-MDS). In some embodiments, the administering to the subject a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt is a treatment of anemia in the subject classified with LR-MDS. In some embodiments, the subject is transfusion dependent (>2 units / 8 weeks) and has isolated anemia (HGB<10g / dL). In some embodiments, the subject has isolated thrombocytopenia based on platelets <20K / L or <50K / L with bleeding. In some embodiments, the subject has isolated neutropenia based on absolute neutrophil count <500. In some embodiments, the subject has multi-lineage cytopenia. In some embodiments, the subject has anemia. In some embodiments, the subject has leukopenia. In some embodiments, the subject has thrombocytopenia. In some embodiments, the treatment restricts iron reducing iron overload. In some embodiments, the MDS is MDS- RS and the subject has one or more somatic mutations of the spliceosome selected from SF3B1, U2AF1, SRSF2 or ZRSR2. In some embodiments, the MDS is MDS-RS with single lineage dysplasia (MDS-RS-SLD) or MDS-RS with multilineage dysplasia (MDS- RS-MLD). In some embodiments, the subject is classified with SF3B1-mutant MDS. In some embodiments, the one or more GlyT1 inhibitor is not bitopertin. In some embodiments, the MDS is other than SF3B1-mutant MDS. In some embodiments, the method further comprises screening for SF3B1 mutation in the subject. In some embodiments, the GlyT1 inhibitor demonstrates an EC50 of less than 500 nM. In some embodiments, the GlyT1 inhibitor demonstrates an EC50 of less than 100 nM. In some embodiments, the subject’s heme levels are substantialy maintained during treatment. In some embodiments, the treatment decreases the subject’s heme levels by no more than 10% (e.g., 10%, 15%, 20%, 25%, and 30%). In some embodiments, the dosage of the pharmaceutical composition does not cause a substantial reduction in heme levels. In some embodiments, the subject has: i) anemia; and i) less than 5% of bone marow blood cels are blasts or immature blood cels. In some embodiments, the subject has: i) anemia; i) below normal erythrocyte numbers and ii) more than 15% of those erythrocytes are sideroblasts. In some embodiments, the subject has: i) anemia; i) below normal blood cel numbers of at least two of erythrocytes, leukocytes and thrombocytes; and, ii) more than 15% of those erythrocytes are sideroblasts. In some embodiments, the subject has: i) anemia; i) below normal blood cel numbers of two or three of erythrocytes, leukocytes and thrombocytes; and, ii) between about 5% to 20 % of bone marow blood cels are immature blood cels or blasts. In some embodiments, the subject has: i) anemia; and i) less than 5% of blood or bone marow cels are immature blood cels or blasts. In some embodiments, the subject has below normal blood cel numbers of two or three of erythrocytes, leukocytes and thrombocytes. In some embodiments, the subject is further receiving blood transfusions and / or growth factor treatment to help blood cels mature. In some embodiments, the subject is further receiving platelet transfusions and / or or growth factor treatment to help blood cels mature. In some embodiments, the subject is further receiving treatment for an infection. In some embodiments, the treatment reduces the blood transfusion and / or platelet transfusion burden. In some embodiments, the GlyT1 inhibitor is a compound having a formula of Formula I, wherein: Ar is unsubstituted or substituted aryl or 6-membered heteroaryl containing one, two or three nitrogen atoms, wherein the substituted aryl and the substituted heteroaryl groups are substituted by one or more substituents selected from the group consisting of hydroxy, halogen, NO2, CN, (C1-C6)-alkyl, (C1-C6)-alkyl substituted by halogen, (C1-C6)-alkyl substituted by hydroxy, (CH2)n—(C1-C6)-alkoxy, (C1- C6)-alkoxy substituted by halogen, NR7R8, C(O)R9, SO2R10, and — C(CH3)═NOR7, or are substituted by a 5-membered aromatic heterocycle containing 1-4 heteroatoms selected from N and O, which is optionaly substituted by (C1-C6)-alkyl;R1 is hydrogen or (C1-C6)-alkyl; R2 is hydrogen, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C1-C6)-alkyl substituted by halogen, (C1- C6)-alkyl substituted by hydroxy, (CH2)n—(C3-C7)-cycloalkyl optionaly substituted by (C1-C6)-alkoxy or by halogen, CH(CH3)—(C3-C7)-cycloalkyl, (CH2)n+1—C(O)—R9, (CH2)n+1—CN, bicyclo[2.2.1]heptyl, (CH2)n+1—O—(C1- C6)-alkyl, (CH2)n-heterocycloalkyl, (CH2)n-aryl or (CH2)n-5 or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur or nitrogen wherein aryl, heterocycloalkyl and heteroaryl are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, halogen, (C1-C6)-alkyl and (C1-C6)-alkoxy; R3, R4 and R6 are each independently hydrogen, hydroxy, halogen, (C1-C6)-alkyl, (C1-C6)- alkoxy or O—(C3-C6)-cycloalkyl; R5 is NO2, CN, C(O)R9 or SO2R10; R7 and R8 are each independently hydrogen or (C1-C6)-alkyl; R9 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8; R10 is (C1-C6)-alkyl optionaly substituted by halogen, (CH2)n—(C3-C6)-cycloalkyl, (CH2)n—(C3-C6)-alkoxy, (CH2)n-heterocycloalkyl or NR7R8; n is 0, 1, or 2; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments, the GlyT1 inhibitor is a compound having a formula of , bitopertin, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments, the pharmaceutical composition further comprises a pharmaceuticaly acceptable carrier. In some embodiments, the subject is a subject in need thereof. In some embodiments, the GlyT1 inhibitor, or pharmaceuticaly acceptable salt thereof, or prodrug of the GlyT1 inhibitor or its pharmaceuticaly acceptable salt, is administered in a therapeuticaly efective amount. In some embodiments, the myelodysplastic syndrome is untreated. In some embodiments, the GlyT1 inhibitor, or pharmaceuticaly acceptable salt thereof, or prodrug of the GlyT1 inhibitor or its pharmaceuticaly acceptable salt is administered as a first line treatment for MDS. In some embodiments, the GlyT1 inhibitor, or pharmaceuticaly acceptable salt thereof, or prodrug of the GlyT1 inhibitor or its pharmaceuticaly acceptable salt is administered as a second line, third line, or fourth line of treatment for the myelodysplastic syndrome. In some embodiments, the myelodysplastic syndrome is subsequent to acute myeloid leukemia. In some embodiments, the treatment increases red blood cel levels. In some embodiments, the treatment increases hemoglobin levels. In some embodiments, the treatment results in an increase in hemoglobin of > 1.5 g / dL for > two weeks. In some embodiments, the treatment results in an increase in hemoglobin of > 1.5 g / dL for > eight weeks. In some embodiments, the subject has been administered one or more blood cel transfusions prior to the start of treatment. In some embodiments, the subject is a low transfusion burden patient. In some embodiments, the patient is a high transfusion burden patient. In some embodiments, the treatment decreases blood cel transfusion burden. In some embodiments, the treatment decreases blood cel transfusion by > 50% for at least four weeks relative to the equal time prior to start of treatment. In some embodiments, the treatment decreases blood cel transfusion by > 50% for at least eight weeks relative to the equal time prior to start of treatment. In some embodiments, the patient has an International Prognostic Scoring System (IPSS) or IPSS-R score of low or intermediate. In some embodiments, the anemia is sideroblastic anemia and the subject has at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% ring blasts as a percentage of bone marow erythroid precursors in subject’s bone marow. In some embodiments, the treatment increases neutrophil levels. In some embodiments, the GlyT1 inhibitor is bitopertin or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments, the method further comprises administering one or more supportive therapy for sideroblastic anemia. In some embodiments, the supportive therapy is transfusion of one or more of: red blood cels, granulocytes, and thrombocytes. In some embodiments, the supportive therapy comprises administration of an iron- chelating agent or multiple iron-chelating agents. In some embodiments, the iron- chelating agent or multiple iron-chelating agents are selected from: a) deferoxamine; b) deferiprone; and c) deferasirox. In some embodiments, the supportive therapy comprises administering an EPO receptor activator. In some embodiments, the EPO receptor activator is selected from: EPO, epoetin alfa, epoetin beta, epoetin delta, epoetin omega, darbepoetin alfa, methoxy- polyethylene-glycol epoetin beta, and synthetic erythropoiesis protein (SEP). In some embodiments, the supportive therapy comprises administration of one or more agents selected from the group consisting of: a G-CSF analog, a GM-CSF analog, an iron-chelating agent, hepcidin or a hepcidin receptor activator, lenalidomide, thalidomide, pomalidomide, azacitidine, decitabine, antithymocyte globulin, and thrombomimetic agent, a histone deacetylase inhibitor, a p38MAPK inhibitor, a glutathione S-transferase π inhibitor, alemtuzumab, a DNA methyltransferase inhibitor, and a histone deacetylase inhibitor. In some embodiments, the supportive therapy comprises administration of one or more agents selected from the group consisting of luspatercept, KER-050 and KER-047. In some embodiments, the treatment decreases iron overload. In some embodiments, the treatment decreases iron content in the liver and / or spleen. Detailed Description of the Disclosure Overview This disclosure relates to pharmaceutical compositions for use in treating (including preventing, reducing progression rate and / or severity of) myelodysplastic syndrome (MDS) and / or one or more complications or symptoms of MDS, wherein the pharmaceutical composition comprises one or more glycine transporter 1 (GlyT1) inhibitor(s), or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt. The methods herein comprise administering the pharmaceutical compositions of this disclosure to a subject in need thereof. In embodiments, an exemplary glycine transporter 1 (GlyT1) inhibitor is bitopertin. The 2016 World Health Organization (WHO) classification system for MDS diferentiates between several subtypes based on the number of dysplastic lineages and cytopenias, the presence of ring sideroblasts, the presence of del (5q), and the presence of excess blasts. Specificaly, methods of this disclosure include treatment of the folowing sub-types of MDS: i) MDS with multilineage dysplasia (MDS-MLD), i) MDS with single lineage dysplasia (MDS-SLD), ii) MDS with ring sideroblasts (MDS-RS), iv) MDS with excess blasts (MDS-EB), and v) unclassifiable MDS. In embodiments, this disclosure does not include use of the present pharmaceutical compositions for treatment of MDS with isolated del(5q) chromosome. MDS has historicaly been risk stratified by use of the International Prognostic Scoring System (IPSS) for MDS, and more recently with the revised-IPSS (IPSS- R). These tools categorize disease risk based on cytogenetic abnormalities, the degree of cytopenias, and the percentage of bone marow blasts. The IPSS-R subdivides patients into five groups (very low-, low-, intermediate-, high-, very high-risk) that difer in terms of survival and risk of leukemic transformation. This is clinicaly relevant as the treatment approach difers between higher-risk and lower-risk patient subgroups. Provided herein are methods and pharmaceutical compositions for the treatment of very low-, low- and intermediate risk MDS, colectively refered to herein as “LR-MDS”. In patients with LR-MDS, the goal of treatment is to improve quality of life by managing the underlying cytopenia and their side efects. The majority of patients are anemic at presentation, and this represents a major clinical chalenge. Accordingly, in one embodiment provided herein are methods for treating one or more symptoms or complications of myelodysplastic syndrome (MDS) including cytopenia such as anemia, leukopenia and thrombocytopenia. In certain embodiments provided herein are methods for the treatment of anemia in a subject classified with LR- MDS comprising administering to the subject a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt. Definitions Unless defined otherwise, al technical and scientific terms have the same meaning as is commonly understood by one of ordinary skil in the art to which the embodiments disclosed belongs. Certain terms are discussed below or elsewhere in the specification to provide additional guidance to the practitioner in describing the compositions and methods of the disclosure and how to make and use them. The scope or meaning of any use of a term wil be apparent from the specific context in which it is used. As used herein, the terms “a” or “an” means that “at least one” or “one or more” unless the context clearly indicates otherwise. As used herein, the term “about” means that the numerical value is approximate and smal variations would not significantly afect the practice of the disclosed embodiments. Where a numerical limitation is used, unless indicated otherwise by the context, “about” means the numerical value can vary by ±10% and remain within the scope of the disclosed embodiments. The term “acyl” is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)-, preferably alkylC(O)-. As used herein, the term “acylamino” means an amino group substituted by an acyl group (e.g., -O-C(=O)-H or -O-C(=O)-alkyl). An example of an acylamino is - NHC(=O)H or -NHC(=O)CH3. The term “lower acylamino” refers to an amino group substituted by a lower acyl group (e.g., -O-C(=O)-H or -O-C(=O)-C1-6alkyl). An example of a lower acylamino is -NHC(=O)H or -NHC(=O)CH3. The term “acyloxy” is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)O-, preferably alkylC(O)O-. As used herein, the term “alkenyl” means a straight or branched alkyl group having one or more double carbon-carbon bonds and 2-20 carbon atoms, including, but not limited to, ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, and 2- butenyl. In some embodiments, the alkenyl chain is from 2 to 10 carbon atoms in length, from 2 to 8 carbon atoms in length, from 2 to 6 carbon atoms in length, or from 2 to 4 carbon atoms in length. The terms “alkoxy”, “phenyloxy”, “benzoxy” and “pyrimidinyloxy” refer to an alkyl group, phenyl group, benzyl group, or pyrimidinyl group, respectively, each optionaly substituted, that is bonded through an oxygen atom. For example, the term “alkoxy” means a straight or branched -O-alkyl group of 1 to 20 carbon atoms, including, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and t-butoxy. In some embodiments, the alkoxy chain is from 1 to 10 carbon atoms in length, from 1 to 8 carbon atoms in length, from 1 to 6 carbon atoms in length, from 1 to 4 carbon atoms in length, from 2 to 10 carbon atoms in length, from 2 to 8 carbon atoms in length, from 2 to 6 carbon atoms in length, or from 2 to 4 carbon atoms in length. As used herein, the term “alkyl” means a saturated hydrocarbon group which is straight-chained or branched. An alkyl group can contain from 1 to 20, from 2 to 20, from 1 to 10, from 2 to 10, from 1 to 8, from 2 to 8, from 1 to 6, from 2 to 6, from 1 to 4, from 2 to 4, from 1 to 3, or 2 or 3 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n- butyl, t-butyl, isobutyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl), hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, decyl, undecyl, dodecyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3- butyl, 2-methyl-1-pentyl, 2,2-dimethyl-1-propyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3- dimethyl-1-butyl, and 2-ethyl-1-butyl. As used herein, the term “alkylamino” means an amino group substituted by an alkyl group having from 1 to 6 carbon atoms. An example of an alkylamino is - NHCH2CH3. As used herein, the term “alkylene” or “alkylenyl” means a divalent alkyl linking group. An example of an alkylene (or alkylenyl) is methylene or methylenyl (-CH2-). As used herein, the term “alkylthio” means an -S-alkyl group having from 1 to 6 carbon atoms. An example of an alkylthio group is -SCH2CH3. As used herein, the term “alkynyl” means a straight or branched alkyl group having one or more triple carbon-carbon bonds and 2-20 carbon atoms, including, but not limited to, acetylene, 1-propylene, and 2-propylene. In some embodiments, the alkynyl chain is 2 to 10 carbon atoms in length, from 2 to 8 carbon atoms in length, from 2 to 6 carbon atoms in length, or from 2 to 4 carbon atoms in length. The term “amide”, as used herein, refers to a group wherein each R30 independently represent a hydrogen or hydrocarbyl group, or two R30 are taken together with the N atom to which they are atached complete a heterocycle having from 4 to 8 atoms in the ring structure. As used herein, the term “amidino” means -C(=NH)NH2. The terms “amine” and “amino” are art-recognized and refer to both unsubstituted and substituted amines and salts thereof, e.g., a moiety that can be represented by wherein each R30 independently represents a hydrogen or a hydrocarbyl group, or two R30 are taken together with the N atom to which they are atached complete a heterocycle having from 4 to 8 atoms in the ring structure. As used herein, the term “aminoalkoxy” means an alkoxy group substituted by an amino group. An example of an aminoalkoxy is -OCH2CH2NH2. As used herein, the term “aminoalkyl” means an alkyl group substituted by an amino group. An example of an aminoalkyl is -CH2CH2NH2. As used herein, the term “aminosulfonyl” means -S(=O)2NH2. As used herein, the term “aminoalkylthio” means an alkylthio group substituted by an amino group. An example of an aminoalkylthio is -SCH2CH2NH2. As used herein, the term “amphiphilic” means a three-dimensional structure having discrete hydrophobic and hydrophilic regions. An amphiphilic compound suitably has the presence of both hydrophobic and hydrophilic elements. As used herein, the term “animal” includes, but is not limited to, humans and non- human vertebrates such as wild, domestic, and farm animals. As used herein, the term “aryl” means a monocyclic, bicyclic, or polycyclic (e.g., having 2, 3 or 4 fused rings) aromatic hydrocarbons. In some embodiments, aryl groups have from 6 to 20 carbon atoms or from 6 to 10 carbon atoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, phenanthrenyl, indanyl, indenyl, and tetrahydronaphthyl. Examples of aryl groups include, but are not limited to:

[0002]

[0003] As used herein, the term “arylalkyl” means a C1-6alkyl substituted by aryl. As used herein, the term “arylamino” means an amino group substituted by an aryl group. An example of an arylamino is -NH(phenyl). As used herein, the term “arylene” means an aryl linking group, i.e., an aryl group that links one group to another group in a molecule. The term “carbamate” is art-recognized and refers to a group wherein R29 and R30 independently represent hydrogen or a hydrocarbyl group, such as an alkyl group, or R29 and R30 taken together with the intervening atom(s) complete a heterocycle having from 4 to 8 atoms in the ring structure. As used herein, the term “carbamoyl” means -C(=O)-NH2. As used herein, the term “carbocycle” means a 5- or 6-membered, saturated or unsaturated cyclic ring, optionaly containing O, S, or N atoms as part of the ring. Examples of carbocycles include, but are not limited to, cyclopentyl, cyclohexyl, cyclopenta-1,3-diene, phenyl, and any of the heterocycles recited above. The term “carbocyclylalkyl”, as used herein, refers to an alkyl group substituted with a carbocycle group. The term “carbonate” is art-recognized and refers to a group -OCO2-R30, wherein R30 represents a hydrocarbyl group. The term “carboxy”, as used herein, refers to a group represented by the formula -CO2H. As used herein, the term “carrier” means a diluent, adjuvant, or excipient with which a compound is administered. Pharmaceutical carriers can be liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, and sesame oil. The pharmaceutical cariers can also be saline, gum acacia, gelatin, starch paste, talc, keratin, coloidal silica, and urea. In addition, auxiliary, stabilizing, thickening, lubricating and coloring agents can be used. As used herein, the term, “compound” means al stereoisomers, tautomers, and isotopes of the compounds described herein. As used herein, the terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”), are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. As used herein, the term “contacting” means bringing together of two elements in an in vitro system or an in vivo system. For example, “contacting” a GlyT1 transporter inhibitor with a GlyT1 transporter with an individual or patient or cel includes the administration of the compound to an individual or patient, such as a human, as wel as, for example, introducing a compound into a sample containing a celular or purified preparation containing the GlyT1 transporter. As used herein, the term “cyano” means -CN. As used herein, the term “cycloalkyl” means non-aromatic cyclic hydrocarbons including cyclized alkyl, alkenyl, and alkynyl groups that contain up to 20 ring-forming carbon atoms. Cycloalkyl groups can include mono- or polycyclic ring systems such as fused ring systems, bridged ring systems, and spiro ring systems. In some embodiments, polycyclic ring systems include 2, 3, or 4 fused rings. A cycloalkyl group can contain from 3 to 15, from 3 to 10, from 3 to 8, from 3 to 6, from 4 to 6, from 3 to 5, or 5 or 6 ring-forming carbon atoms. Ring-forming carbon atoms of a cycloalkyl group can be optionaly substituted by oxo or sulfido. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbornyl, norpinyl, norcarnyl, and adamantyl. Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused (having a bond in common with) to the cycloalkyl ring, for example, benzo or thienyl derivatives of pentane, pentene, hexane, and the like (e.g., 2,3-dihydro-1H-indene-1-yl, or 1H-inden-2(3H)-one-1-yl). As used herein, the term “cycloalkylalkyl” means a C1-6alkyl substituted by cycloalkyl. As used herein, the term “dialkylamino” means an amino group substituted by two alkyl groups, each having from 1 to 6 carbon atoms. As used herein, the term “diazamino” means -N(NH2)2. The term “ester”, as used herein, refers to a group -C(O)OR30 wherein R30 represents a hydrocarbyl group. The term “ether”, as used herein, refers to a hydrocarbyl group linked through an oxygen to another hydrocarbyl group. Accordingly, an ether substituent of a hydrocarbyl group may be hydrocarbyl-O-. Ethers may be either symmetrical or unsymmetrical. Examples of ethers include, but are not limited to, heterocycle-O-heterocycle and aryl-O- heterocycle. Ethers include “alkoxyalkyl” groups, which may be represented by the general formula alkyl-O-alkyl. As used herein, the term “facialy amphiphilic” or “facial amphiphilicity” means compounds with polar (hydrophilic) and nonpolar (hydrophobic) side chains that adopt conformation(s) leading to segregation of polar and nonpolar side chains to opposite faces or separate regions of the structure or molecule. As used herein, the term “glycine transporter” or “GlyT” refers to membrane protein that facilitates the transport of glycine across the plasma membrane of a cel. Non-limiting examples of glycine transports include glycine transporter 1 (GlyT1) and glycine transporter 2 (GlyT2). As used herein, the term “GlyT1” or “GlyT1 transporter” means sodium- and chloride-dependent glycine transporter 1, also known as glycine transporter 1, is a protein that in humans is encoded by the SLC6A9 gene (Kim KM, Kingsmore SF, Han H, Yang- Feng TL, Godinot N, Seldin MF, Caron MG, Giros B (Jun 1994). "Cloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes". Mol Pharmacol.45 (4): 608–17; Jones EM, Fernald A, Bel GI, Le Beau MM (Nov 1995). "Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization". Cytogenet Cel Genet.71 (3): 211), which is hereby incorporated by reference in its entirety. As used herein, the term “GlyT2” or “GlyT2 transporter” means sodium- and chloride-dependent glycine transporter 2, also known as glycine transporter 2, is a protein that in humans is encoded by the SLC6A5 gene (Morow JA, Colie IT, Dunbar DR, Walker GB, Shahid M, Hil DR (November 1998). "Molecular cloning and functional expression of the human glycine transporter GlyT2 and chromosomal localisation of the gene in the human genome". FEBS Let.439 (3): 334–40). As used herein, the term “GlyT1 inhibitor” means a compound that inhibits or blocks the activity of GlyT1 transporter including compounds inhibiting the activity of any isoform of GlyT1. Non-limiting examples of GlyT1 inhibitors are provided herein. In some embodiments, the GlyT1 inhibitor is a specific GlyT1 inhibitor, which means that the inhibitor has an inhibitor activity that is greater for GlyT1 as compared to GlyT2. In some embodiments, the inhibitor inhibits GlyT1 as compared to GlyT2 with at least, or about, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% selectivity. In some embodiments, the GlyT1 inhibitor inhibits GlyT1 but does not inhibit or significantly inhibit the activity of GlyT2. A GlyT1 inhibitor that does not significantly inhibit the activity of GlyT2 if it inhibits the activity of GlyT2 less than 5%, 4%, 3%, 2%, or 1%. The selectivity ofGlyT1 inhibitor is determined based on the known assays in the art such as the assays described in the published journal article (B. N. Atkinson, S. C. Bel, M. De Vivo, L. R. Kowalski, S. M. Lechner, V. I. Ognyanov, C.-S. Tham, C. Tsai, J. Jia, D. Ashton and M. A. Klitenick, ALX 5407: A Potent, Selective Inhibitor of the hGlyT1 Glycine Transporter, Molecular Pharmacology December 2001, 60 (6) 1414-1420). As used herein, the term “GlyT2 inhibitor” means a compound that inhibits or blocks the activity of GlyT2 transporter including compounds inhibiting the activity of any isoform of GlyT2. In some embodiments, the GlyT2 inhibitor is a non-specific inhibitor, which means that it can also inhibit or block the activity of GlyT1. In some embodiments, the GlyT2 inhibitor is a specific GlyT2 inhibitor, which means that the inhibitor has an inhibitor activity that is greater for GlyT2 as compared to GlyT1. In some embodiments, the inhibitor inhibits GlyT2 as compared to GlyT1 with at least, or about, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%,.98%, 99% selectivity. In some embodiments, the GlyT2 inhibitor inhibits GlyT2 activity but does not inhibit or significantly inhibit the activity of GlyT1. A GlyT2 inhibitor that does not significantly inhibit the activity of GlyT1 if it inhibits the activity of GlyT1 less than 5%, 4%, 3%, 2%, or 1%. The selectivity ofGlyT2 inhibitor is determined based on the known assays in the art such as the assays based described in the published journal article (B. N. Atkinson, S. C. Bel, M. De Vivo, L. R. Kowalski, S. M. Lechner, V. I. Ognyanov, C.-S. Tham, C. Tsai, J. Jia, D. Ashton and M. A. Klitenick, ALX 5407: A Potent, Selective Inhibitor of the hGlyT1 Glycine Transporter, Molecular Pharmacology December 2001, 60 (6) 1414-1420), which is incorporated by its entirety. As used herein, the term “guanidino” means -NH(=NH)NH2. As used herein, the term “halo” means halogen groups including, but not limited to fluoro, chloro, bromo, and iodo. As used herein, the term “haloalkoxy” means an -O-haloalkyl group. An example of an haloalkoxy group is OCF3. As used herein, the term “haloalkyl” means a C1-6alkyl group having one or more halogen substituents. Examples of haloalkyl groups include, but are not limited to, CF3, C2F5, CH2F, CHF2, CCl3, CHCl2, and CH2CF3. As used herein, the term “heteroaryl” means an aromatic heterocycle having up to 20 ring-forming atoms (e.g., C) and having at least one heteroatom ring member (ring- forming atom) such as sulfur, oxygen, or nitrogen. In some embodiments, the heteroaryl group has at least one or more heteroatom ring-forming atoms, each of which is, independently, sulfur, oxygen, or nitrogen. In some embodiments, the heteroaryl group has from 3 to 20 ring-forming atoms, from 3 to 10 ring-forming atoms, from 3 to 6 ring- forming atoms, or from 3 to 5 ring-forming atoms. In some embodiments, the heteroaryl group contains 2 to 14 carbon atoms, from 2 to 7 carbon atoms, or 5 or 6 carbon atoms. In some embodiments, the heteroaryl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, or 1 or 2 heteroatoms. Heteroaryl groups include monocyclic and polycyclic (e.g., having 2, 3 or 4 fused rings) systems. Examples of heteroaryl groups include, but are not limited to, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, quinolyl, isoquinolyl, thienyl, imidazolyl, thiazolyl, indolyl (such as indol-3-yl), pyroyl, oxazolyl, benzofuryl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4- thiadiazolyl, isothiazolyl, benzothienyl, purinyl, carbazolyl, benzimidazolyl, indolinyl, pyranyl, oxadiazolyl, isoxazolyl, triazolyl, thianthrenyl, pyrazolyl, indolizinyl, isoindolyl, isobenzofuranyl, benzoxazolyl, xanthenyl, 2H-pyrolyl, pyrolyl, 3H-indolyl, 4H- quinolizinyl, phthalazinyl, naphthyridinyl, quinazolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, isoxazolyl, furanyl, and phenoxazinyl groups. Suitable heteroaryl groups include 1,2,3-triazole, 1,2,4- triazole, 5-amino-1,2,4-triazole, imidazole, oxazole, isoxazole, 1,2,3-oxadiazole, 1,2,4- oxadiazole, 3-amino-1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, pyridine, and 2-aminopyridine. As used herein, the term “heteroarylalkyl” means a C1-6alkyl group substituted by a heteroaryl group. As used herein, the term “heteroarylamino” means an amino group substituted by a heteroaryl group. An example of a heteroarylamino is -NH-(2-pyridyl). As used herein, the term “heteroarylene” means a heteroaryl linking group, i.e., a heteroaryl group that links one group to another group in a molecule. The term “heteroatom” as used herein means an atom of any element other than carbon or hydrogen. Exemplary heteroatoms are nitrogen, oxygen, and sulfur. As used herein, the term “heterocycle” or “heterocyclic ring” means a 5- to 7- membered mono- or bicyclic or 7- to 10-membered bicyclic heterocyclic ring system any ring of which may be saturated or unsaturated, and which consists of carbon atoms and from one to three heteroatoms chosen from N, O and S, and wherein the N and S heteroatoms may optionaly be oxidized, and the N heteroatom may optionaly be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. Particularly useful are rings containing one oxygen or sulfur, one to three nitrogen atoms, or one oxygen or sulfur combined with one or two nitrogen atoms. The heterocyclic ring may be atached at any heteroatom or carbon atom which results in the creation of a stable structure. Examples of heterocyclic groups include, but are not limited to, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2- oxopiperidinyl, 2-oxopyrolodinyl, 2-oxoazepinyl, azepinyl, pyrolyl, 4-piperidonyl, pyrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, thiadiazoyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl. Morpholino is the same as morpholinyl. As used herein, the term “heterocycloalkyl” means non-aromatic heterocycles having up to 20 ring-forming atoms including cyclized alkyl, alkenyl, and alkynyl groups, where one or more of the ring-forming carbon atoms is replaced by a heteroatom such as an O, N, or S atom. Hetercycloalkyl groups can be mono or polycyclic (e.g., fused, bridged, or spiro systems). In some embodiments, the heterocycloalkyl group has from 1 to 20 carbon atoms, or from 3 to 20 carbon atoms. In some embodiments, the heterocycloalkyl group contains 3 to 14 ring-forming atoms, 3 to 7 ring-forming atoms, or 5 or 6 ring-forming atoms. In some embodiments, the heterocycloalkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, or 1 or 2 heteroatoms. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 triple bonds. Examples of heterocycloalkyl groups include, but are not limited to, morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, 2,3-dihydrobenzofuryl, 1,3-benzodioxole, benzo- 1,4-dioxane, piperidinyl, pyrolidinyl, isoxazolidinyl, oxazolidinyl, isothiazolidinyl, pyrazolidinyl, thiazolidinyl, imidazolidinyl, and pyrolidin-2-one-3-yl. In addition, ring- forming carbon atoms and heteroatoms of a heterocycloalkyl group can be optionaly substituted by oxo or sulfido. For example, a ring-forming S atom can be substituted by 1 or 2 oxo (form a S(O) or S(O)2). For another example, a ring-forming C atom can be substituted by oxo (form carbonyl). Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (having a bond in common with) to the nonaromatic heterocyclic ring including, but not limited to, pyridinyl, thiophenyl, phthalimidyl, naphthalimidyl, and benzo derivatives of heterocycles such as indolene, isoindolene, 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-yl, 5,6-dihydrothieno[2,3- c]pyridin-7(4H)-one-5-yl, isoindolin-1-one-3-yl, and 3,4-dihydroisoquinolin-1(2H)-one- 3yl groups. Ring-forming carbon atoms and heteroatoms of the heterocycloalkyl group can be optionaly substituted by oxo or sulfido. As used herein, the term “heterocycloalkylalkyl” refers to a C1-6alkyl substituted by heterocycloalkyl. As used herein, the term “hydroxy” or “hydroxyl” means an -OH group. As used herein, the term “hydroxyalkyl” or “hydroxylalkyl” means an alkyl group substituted by a hydroxyl group. Examples of a hydroxylalkyl include, but are not limited to, -CH2OH and -CH2CH2OH. As used herein, the term “individual” or “patient,” used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, catle, sheep, horses, or primates, such as humans. As used herein, the phrase “inhibiting activity,” such as enzymatic or transporter activity means reducing by any measurable amount the activity of an enzyme or transporter, such as the GlyT1 transporter. As used herein, the phrase “in need thereof” means that the animal or mammal has been identified as having a need for the particular method or treatment. In some embodiments, the identification can be by any means of diagnosis. In any of the methods and treatments described herein, the animal or mammal can be in need thereof. In some embodiments, the animal or mammal is in an environment or wil be traveling to an environment in which a particular disease, disorder, or condition is prevalent. As used herein, the phrase “in situ gelable” means embracing not only liquids of low viscosity that form gels upon contact with the eye or with lacrimal fluid in the exterior of the eye, but also more viscous liquids such as semi-fluid and thixotropic gels that exhibit substantialy increased viscosity or gel stifness upon administration to the eye. As used herein, the phrase “integer from X to Y” means any integer that includes the endpoints. For example, the phrase “integer from X to Y” means 1, 2, 3, 4, or 5. The term “lower” when used in conjunction with a chemical moiety, such as, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy is meant to include groups where there are ten or fewer non-hydrogen atoms in the substituent, preferably six or fewer. A “lower alkyl”, for example, refers to an alkyl group that contains ten or fewer carbon atoms, preferably six or fewer. In certain embodiments, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy substituents defined herein are respectively lower acyl, lower acyloxy, lower alkyl, lower alkenyl, lower alkynyl, or lower alkoxy, whether they appear alone or in combination with other substituents, such as in the recitations hydroxyalkyl and aralkyl (in which case, for example, the atoms within the aryl group are not counted when counting the carbon atoms in the alkyl substituent). As used herein, the term “mammal” means a rodent (i.e., a mouse, a rat, or a guinea pig), a monkey, a cat, a dog, a cow, a horse, a pig, or a human. In some embodiments, the mammal is a human. As used herein, the term “N-alkyl” refers to a alkyl chain that is substituted with an amine group. Non-limiting examples, include, but are not limited to . The alkyl chain can be linear, branched, cyclic, or any combination thereof. In some embodiments, the alkyl comprises 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2 carbons. As used herein, the term “nitro” means -NO2. As used herein, the term “n-membered”, where n is an integer, typicaly describes the number of ring-forming atoms in a moiety, where the number of ring-forming atoms is n. For example, pyridine is an example of a 6-membered heteroaryl ring and thiophene is an example of a 5-membered heteroaryl ring. As used herein, the phrase “optionaly substituted” means that substitution is optional and therefore includes both unsubstituted and substituted atoms and moieties. A “substituted” atom or moiety indicates that any hydrogen on the designated atom or moiety can be replaced with a selection from the indicated substituent groups, provided that the normal valency of the designated atom or moiety is not exceeded, and that the substitution results in a stable compound. For example, if a methyl group is optionaly substituted, then 3 hydrogen atoms on the carbon atom can be replaced with substituent groups. As used herein, the phrase “pharmaceuticaly acceptable” means those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with tissues of humans and animals. In some embodiments, “pharmaceuticaly acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generaly recognized pharmacopeia for use in animals, and more particularly in humans. A “pharmaceuticaly acceptable salt” is intended to mean a salt of a free acid or base of a compound represented herein that is non-toxic, biologicaly tolerable, or otherwise biologicaly suitable for administration to the subject. See, generaly, S.M. Berge, et al., “Pharmaceutical Salts,” J. Pharm. Sci., 1977, 66, 1-19. Prefered pharmaceuticaly acceptable salts are those that are pharmacologicaly effective and suitable for contact with the tissues of subjects without undue toxicity, iritation, or alergic response. A compound described herein may possess a suficiently acidic group, a suficiently basic group, both types of functional groups, or more than one of each type, and accordingly react with a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceuticaly acceptable salt. For a compound described herein that contains a basic group, such as an amine, a pharmaceuticaly acceptable salt may be prepared by any suitable method available in the art, for example, treatment of the free base with an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, nitric acid, boric acid, and phosphoric acid, or with an organic acid, such as acetic acid, phenylacetic acid, propionic acid, stearic acid, lactic acid, ascorbic acid, maleic acid, hydroxymaleic acid, isethionic acid, succinic acid, valeric acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, oleic acid, palmitic acid, lauric acid, a pyranosidyl acid, such as glucuronic acid or galacturonic acid, an alpha-hydroxy acid, such as mandelic acid, citric acid, or tartaric acid, an amino acid, such as aspartic acid or glutamic acid, an aromatic acid, such as benzoic acid, 2-acetoxybenzoic acid, naphthoic acid, or cinnamic acid, a sulfonic acid, such as laurylsulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, or ethanesulfonic acid, or any compatible mixture of acids such as those given as examples herein, and any other acid and mixture thereof that are regarded as equivalents or acceptable substitutes in light of the ordinary level of skil in this technology. For a compound described herein that contains an acidic group, such as a carboxylic acid group, base addition salts can be prepared by any suitable method available in the art, for example, treatment of such compound with a suficient amount of the desired the desired base, either neat or in a suitable inert solvent. Examples of pharmaceuticaly acceptable base addition salts include, but are not limited to, lithium, sodium, potassium, calcium, ammonium, zinc, or magnesium salt, or other metal salts; organic amino salts, such as, alkyl, dialkyl, trialkyl, or tetra-alkyl ammonium salts. Other examples of pharmaceuticaly acceptable salts include, but are not limited to, camsylate, sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen-phosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-1,4-dioates, hexyne-1,6- dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, methylsulfonates, propylsulfonates, besylates, xylenesulfonates, naphthalene-1-sulfonates, naphthalene-2- sulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, γ- hydroxybutyrates, glycolates, tartrates, and mandelates. Lists of other suitable pharmaceuticaly acceptable salts are found in Remington's Pharmaceutical Sciences, 17th Edition, Mack Publishing Company, Easton, Pa., 1985. The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound difers from the various salt forms in certain physical properties, such as solubility in polar solvents, but otherwise the salts are equivalent to the parent form of the compound for the purposes of the present application. As used herein, the term “phenyl” means -C6H5. A phenyl group cn be unsubstituted or substituted with one, two, or three suitable substituents. The terms “polycyclyl”, “polycycle”, and “polycyclic” refer to two or more rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls) in which two or more atoms are common to two adjoining rings, e.g., the rings are “fused rings”. Each of the rings of the polycycle can be substituted or unsubstituted. In certain embodiments, each ring of the polycycle contains from 3 to 10 atoms in the ring, preferably from 5 to 7. As used herein, the term “prodrug” means a derivative of a known direct acting drug, which derivative has enhanced delivery characteristics and therapeutic value as compared to the drug, and is transformed into the active drug by an enzymatic or chemical process. A common method for making a prodrug is to include one or more selected moieties which are hydrolyzed under physiologic conditions to yield the desired molecule. In certain embodiments, the prodrug is converted by an enzymatic activity of the host animal. For example, a prodrug with a nitro group on an aromatic ring could be reduced by reductase to generate the desired amino group of the coresponding active compound in vivo. In another example, functional groups such as a hydroxyl, carbonate, or carboxylic acid in the parent compound are presented as an ester, which could be cleaved by esterases. Additionaly, amine groups in the parent compounds are presented in, but not limited to, carbamate, N-alkylated or N-acylated forms (Simplício et al, “Prodrugs for Amines,” Molecules, (2008), 13:519-547). In certain embodiments, some or al of the compounds of described herein in a formulation represented above can be replaced with the corresponding suitable prodrug. As used herein, the term “purified” means that when isolated, the isolate contains at least 90%, at least 95%, at least 98%, or at least 99% of a compound described herein by weight of the isolate. As used herein, the phrase “quaternary ammonium salts” means derivatives of the disclosed compounds with one or more tertiary amine moieties wherein at least one of the tertiary amine moieties in the parent compound is modified by converting the tertiary amine moiety to a quaternary ammonium cation via alkylation (and the cations are balanced by anions such as Cl-, CH3COO-, and CF3COO-), for example methylation or ethylation. As used herein, the term “semicarbazone” means =NNHC(=O)NH2. As used herein, the phrase “solubilizing agent” means agents that result in formation of a micelar solution or a true solution of the drug. As used herein, the term “solution / suspension” means a liquid composition wherein a first portion of the active agent is present in solution and a second portion of the active agent is present in particulate form, in suspension in a liquid matrix. As used herein, the phrase “substantialy isolated” means a compound that is at least partialy or substantialy separated from the environment in which it is formed or detected The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons of the backbone. It wil be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permited valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term “substituted” is contemplated to include al permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or diferent for appropriate organic compounds. For purposes of this application, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. Substituents can include any substituents described herein, for example, a halogen, a hydroxyl, a carbonyl (such as a carboxyl, an alkoxycarbonyl, a formyl, or an acyl), a thiocarbonyl (such as a thioester, a thioacetate, or a thioformate), an alkoxyl, a phosphoryl, a phosphate, a phosphonate, a phosphinate, an amino, an amido, an amidine, an imine, a cyano, a nitro, an azido, a sulfhydryl, an alkylthio, a sulfate, a sulfonate, a sulfamoyl, a sulfonamido, a sulfonyl, a heterocyclyl, an aralkyl, or an aromatic or heteroaromatic moiety. It wil be understood by those skiled in the art that substituents can themselves be substituted, if appropriate. Unless specificaly stated as “unsubstituted,” references to chemical moieties herein are understood to include substituted variants. For example, reference to an “aryl” group or moiety implicitly includes both substituted and unsubstituted variants. The term “sulfate” is art-recognized and refers to the group -OSO3H, or a pharmaceuticaly acceptable salt thereof. The term “sulfonamide” is art-recognized and refers to the group represented by the general formulae wherein R29 and R30 independently represents hydrogen or hydrocarbyl, such as alkyl, or R29 and R30 taken together with the intervening atom(s) complete a heterocycle having from 4 to 8 atoms in the ring structure. The term “sulfoxide” is art-recognized and refers to the group -S(O)-R30, wherein R30 represents a hydrocarbyl. The term “sulfonate” is art-recognized and refers to the group SO3H, or a pharmaceuticaly acceptable salt thereof. The term “sulfone” is art-recognized and refers to the group -S(O)2-R30, wherein R30 represents a hydrocarbyl. As used herein, the phrase “therapeuticaly efective amount” means the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response that is being sought in a tissue, system, animal, individual or human by a researcher, veterinarian, medical doctor or other clinician. The therapeutic efect is dependent upon the disorder being treated or the biological efect desired. As such, the therapeutic efect can be a decrease in the severity of symptoms associated with the disorder and / or inhibition (partial or complete) of progression of the disorder, or improved treatment, healing, prevention or elimination of a disorder, or side-effects. The amount needed to elicit the therapeutic response can be determined based on the age, health, size and sex of the subject. Optimal amounts can also be determined based on monitoring of the subject’s response to treatment. The term “thioalkyl”, as used herein, refers to an alkyl group substituted with a thiol group. The term “thioester”, as used herein, refers to a group -C(O)SR30 or -SC(O)R30 wherein R30 represents a hydrocarbyl. The term “thioether”, as used herein, is equivalent to an ether, wherein the oxygen is replaced with a sulfur. As used herein, the terms “treat,” “treated,” or “treating” mean both therapeutic treatment and prophylactic measures wherein the object is to slow down (lessen) an undesired physiological condition, disorder or disease, or obtain beneficial or desired clinical results. Beneficial or desired clinical results include, but are not limited to, aleviation of symptoms; diminishment of extent of condition, disorder or disease; stabilized (i.e., not worsening) state of condition, disorder or disease; delay in onset or slowing of condition, disorder or disease progression; amelioration of the condition, disorder or disease state or remission (whether partial or total), whether detectable or undetectable; an amelioration of at least one measurable physical parameter, not necessarily discernible by the patient; or enhancement or improvement of condition, disorder or disease. Treatment includes eliciting a clinicaly significant response without excessive levels of side efects. Treatment also includes prolonging survival as compared to expected survival if not receiving treatment. Thus, “treatment of MDS” means an activity that aleviates or ameliorates any of the primary phenomena or secondary symptoms associated with the MDS or other conditions described herein. The term “urea” is art-recognized and may be represented by the general formula wherein R29 and R30 independently represent hydrogen or a hydrocarbyl, such as alkyl, or either occurence of R29 taken together with R30 and the intervening atom(s) complete a heterocycle having from 4 to 8 atoms in the ring structure. At various places in the present specification, substituents of compounds may be disclosed in groups or in ranges. It is specificaly intended that embodiments include each and every individual subcombination of the members of such groups and ranges. For example, the term “C1-6alkyl” is specificaly intended to individualy disclose methyl, ethyl, propyl, C4alkyl, C5alkyl, and C6alkyl. For compounds in which a variable appears more than once, each variable can be a diferent moiety selected from the Markush group defining the variable. For example, where a structure is described having two R groups that are simultaneously present on the same compound, the two R groups can represent diferent moieties selected from the Markush groups defined for R. In another example, when an optionaly multiple substituent is designated in the form, for example, , then it is understood that substituent R can occur s number of times on the ring, and R can be a diferent moiety at each occurence. In the above example, where the variable T1 is defined to include hydrogens, such as when T1 is CH2, NH, etc., any H can be replaced with a substituent. It is further appreciated that certain features described herein, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable sub-combination. It is understood that the present embodiments encompasses the use, where applicable, of stereoisomers, diastereomers and optical stereoisomers of the compounds, as wel as mixtures thereof. Additionaly, it is understood that stereoisomers, diastereomers, and optical stereoisomers of the compounds, and mixtures thereof, are within the scope of the embodiments. By way of non-limiting example, the mixture may be a racemate or the mixture may comprise unequal proportions of one particular stereoisomer over the other. Additionaly, the compounds can be provided as a substantialy pure stereoisomers, diastereomers and optical stereoisomers (such as epimers). The compounds described herein can be asymmetric (e.g., having one or more stereocenters). Al stereoisomers, such as enantiomers and diastereomers, are intended to be included within the scope of the embodiments unless otherwise indicated. Compounds that contain asymmetricaly substituted carbon atoms can be isolated in opticaly active or racemic forms. Methods of preparation of opticaly active forms from opticaly active starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, and C=N double bonds, can also be present in the compounds described herein, and al such stable isomers are provided herein. Cis and trans geometric isomers of the compounds are also included within the present embodiments and can be isolated as a mixture of isomers or as separated isomeric forms. Where a compound capable of stereoisomerism or geometric isomerism is designated in its structure or name without reference to specific R / S or cis / trans configurations, it is intended that al such isomers are contemplated. In some embodiments, the composition comprises a compound, or a pharmaceuticaly acceptable salt, solvate or prodrug thereof, that is at least 90%, at least 95%, at least 98%, or at least 99%, or 100% enantiomeric pure, which means that the ratio of one enantiomer to the other in the composition is at least 90:1 at least 95:1, at least 98:1, or at least 99:1, or is completely in the form of one enantiomer over the other. In certain embodiments, the compound enriched in one enantiomer is substantialy free of the other enantiomer, wherein substantialy free means that the substance in question makes up less than 10%, or less than 5%, or less than 4%, or less than 3%, or less than 2%, or less than 1% as compared to the amount of the other enantiomer, e.g., in the composition or compound mixture. For example, if a composition or compound mixture contains 98 grams of a first enantiomer and 2 grams of a second enantiomer, it would be said to contain 98 mol percent of the first enantiomer and only 2% of the second enantiomer. In certain embodiments, the compound enriched in one enantiomer is substantialy free of the other enantiomer, wherein substantialy free means that the substance in question makes up less than 10%, or less than 5%, or less than 4%, or less than 3%, or less than 2%, or less than 1% as compared to the amount of the other enantiomer, e.g., in the composition or compound mixture. For example, if a composition or compound mixture contains 98 grams of a first enantiomer and 2 grams of a second enantiomer, it would be said to contain 98 mol percent of the first enantiomer and only 2% of the second enantiomer. Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art, including, for example, chiral HPLC, fractional recrystalization using a chiral resolving acid which is an opticaly active, salt-forming organic acid. Suitable resolving agents for fractional recrystalization methods include, but are not limited to, opticaly active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, and the various opticaly active camphorsulfonic acids such as β-camphorsulfonic acid. Other resolving agents suitable for fractional crystalization methods include, but are not limited to, stereoisomericaly pure forms of α-methylbenzylamine (e.g., S and R forms, or diastereomericaly pure forms), 2-phenylglycinol, norephedrine, ephedrine, N- methylephedrine, cyclohexylethylamine, and 1,2-diaminocyclohexane. Resolution of racemic mixtures can also be carried out by elution on a column packed with an opticaly active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent compositions can be determined by one skiled in the art. Compounds may also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Examples of prototropic tautomers include, but are not limited to, ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, amide-imidic acid pairs, enamine-imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system including, but not limited to, 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H- isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or stericaly locked into one form by appropriate substitution. Glycine transporter inhibitors, such as GlyT1 inhibitors, including their pharmaceuticaly acceptable salts (e.g., the GlyT1 inhibitors as disclosed herein) can also exist as hydrates and solvates, as wel as anhydrous and non-solvated forms. A “hydrate” is a compound that exists in a composition with water molecules. The composition can include water in stoichiometric quantities, such as a monohydrate or a dihydrate, or can include water in random amounts. A “solvate” is a similar composition except that a solvent other that water, such as with methanol, ethanol, dimethylformamide, and diethyl ether, replaces the water. For example, methanol or ethanol can form an “alcoholate,"” which can again be stoichiometic or non-stoichiometric. Mixtures of such solvates or hydrates can also be prepared. The source of such solvate or hydrate can be from the solvent of crystalization, inherent in the solvent of preparation or crystalization, or adventitious to such solvent. The compounds of the application, including their pharmaceuticaly acceptable salts and prodrugs, can exist as various polymorphs, pseudo-polymorphs, or in amorphous state. The term “polymorph”, as used herein, refers to diferent crystaline forms of the same compound and other solid state molecular forms including pseudo-polymorphs, such as hydrates, solvates, or salts of the same compound. Diferent crystaline polymorphs have diferent crystal structures due to a diferent packing of molecules in the latice, as a result of changes in temperature, pressure, or variations in the crystalization process. Polymorphs difer from each other in their physical properties, such as x-ray difraction characteristics, stability, melting points, solubility, or rates of dissolution in certain solvents. Thus crystaline polymorphic forms are important aspects in the development of suitable dosage forms in pharmaceutical industry. Compounds can also include al isotopes of atoms occuring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but diferent mass numbers. For example, isotopes of hydrogen include tritium and deuterium. In some embodiments, the compounds, or salts thereof, are substantialy isolated. Partial separation can include, for example, a composition enriched in the compound. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compound, or salt thereof. Methods for isolating compounds and their salts are routine in the art. Although the disclosed compounds are suitable, other functional groups can be incorporated into the compound with an expectation of similar results. In particular, thioamides and thioesters are anticipated to have very similar properties. The distance between aromatic rings can impact the geometrical patern of the compound and this distance can be altered by incorporating aliphatic chains of varying length, which can be optionaly substituted or can comprise an amino acid, a dicarboxylic acid or a diamine. The distance between and the relative orientation of monomers within the compounds can also be altered by replacing the amide bond with a surogate having additional atoms. Thus, replacing a carbonyl group with a dicarbonyl alters the distance between the monomers and the propensity of dicarbonyl unit to adopt an anti-arangement of the two carbonyl moiety and alter the periodicity of the compound. Pyromelitic anhydride represents stil another alternative to simple amide linkages which can alter the conformation and physical properties of the compound. Modern methods of solid phase organic chemistry (E. Atherton and R. C. Sheppard, Solid Phase Peptide Synthesis A Practical Approach IRL Press Oxford 1989) now alow the synthesis of homodisperse compounds with molecular weights approaching 5,000 Daltons. Other substitution paterns are equaly efective. The compounds also include derivatives refered to as prodrugs. Compounds containing an amine function can also form N-oxides. A reference herein to a compound that contains an amine function also includes the N-oxide. Where a compound contains several amine functions, one or more than one nitrogen atom can be oxidized to form an N-oxide. Examples of N-oxides include N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle. N-Oxides can be formed by treatment of the coresponding amine with an oxidizing agent such as hydrogen peroxide or a per-acid (e.g., a peroxycarboxylic acid) (see, Advanced Organic Chemistry, by Jery March, 4th Edition, Wiley Interscience). By hereby reserving the right to proviso out or exclude any individual members of any such group, including any sub-ranges or combinations of sub-ranges within the group, that can be claimed according to a range or in any similar manner, less than the ful measure of this disclosure can be claimed for any reason. Further, by hereby reserving the right to proviso out or exclude any individual substituents, analogs, compounds, ligands, structures, or groups thereof, or any members of a claimed group, less than the ful measure of this disclosure can be claimed for any reason. Throughout this disclosure, various patents, patent applications and publications are referenced. The disclosures of these patents, patent applications and publications in their entireties are incorporated into this disclosure by reference in order to more fuly describe the state of the art as known to those skiled therein as of the date of this disclosure. This disclosure wil govern in the instance that there is any inconsistency between the patents, patent applications and publications cited and this disclosure. For convenience, certain terms employed in the specification, examples and claims are colected here. Unless defined otherwise, al technical and scientific terms used in this disclosure have the same meanings as commonly understood by one of ordinary skil in the art to which this disclosure belongs. Embodiments of various compounds and salts thereof are provided. Where a variable is not specificaly recited, the variable can be any option described herein, except as otherwise noted or dictated by context. In some embodiments, the compound is as described in the appended exemplary, non-limiting claims, or a pharmaceuticaly acceptable salt, solvate or prodrug thereof. Glycine Transporter 1 (GlyT1) Inhibitors of the Disclosure and Compositions Thereof In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula I, Formula I, wherein: Ar is unsubstituted or substituted aryl or 6-membered heteroaryl containing one, two or three nitrogen atoms, wherein the substituted aryl and the substituted heteroaryl groups are substituted by one or more substituents selected from the group consisting of hydroxy, halogen, NO2, CN, (C1-C6)-alkyl, (C1-C6)-alkyl substituted by halogen, (C1-C6)-alkyl substituted by hydroxy, (CH2)n—(C1-C6)-alkoxy, (C1- C6)-alkoxy substituted by halogen, NR7R8, C(O)R9, SO2R10, and — C(CH3)═NOR7, or are substituted by a 5-membered aromatic heterocycle containing 1-4 heteroatoms selected from N and O, which is optionaly substituted by (C1-C6)-alkyl; R1 is hydrogen or (C1-C6)-alkyl; R2 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkenyl, (C1-C6)-alkyl substituted by halogen, (C1- C6)-alkyl substituted by hydroxy, (CH2)n—(C3-C7)-cycloalkyl optionaly substituted by (C1-C6)-alkoxy or by halogen, CH(CH3)—(C3-C7)-cycloalkyl, (CH2)n+1—C(O)—R9, (CH2)n+1—CN, bicyclo[2.2.1]heptyl, (CH2)n+1—O—(C1- C6)-alkyl, (CH2)n-heterocycloalkyl, (CH2)n-aryl or (CH2)n-5 or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur or nitrogen wherein aryl, heterocycloalkyl and heteroaryl are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, halogen, (C1-C6)-alkyl and (C1-C6)-alkoxy; R3, R4 and R6 are each independently hydrogen, hydroxy, halogen, (C1-C6)-alkyl, (C1-C6)- alkoxy or O—(C3-C6)-cycloalkyl; R5 is NO2, CN, C(O)R9 or SO2R10; R7 and R8 are each independently hydrogen or (C1-C6)-alkyl; R9 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8; R10 is (C1-C6)-alkyl optionaly substituted by halogen, (CH2)n—(C3-C6)-cycloalkyl, (CH2)n—(C3-C6)-alkoxy, (CH2)n-heterocycloalkyl or NR7R8; n is 0, 1, or 2; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of , bitopertin, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In certain embodiments, the patients are not from the SF3B1mut subpopulation of MDS patients as bitopertin may be contra-indicated in such patients. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula I, Formula I, wherein: R1 represents a heteroaryl selected from the group consisting of: imidazolyl, thiazolyl, pyridyl, oxazolyl, pyrazolyl, triazolyl, oxadiazolyl, quinolinyl, isoxazolyl, pyroloimidazoyl, and thiadiazole, wherein said heteroaryl is optionaly substituted by one or more substituents selected from -OH, -NR7R8, halogen, (C1- C8)alkyl, (C3-C10)cycloalkyl, (C1-C8)alkoxy, (C1- C12)alkoxyalkyl, (C1- C8)hydroxyalkyl, (C6-C14)aryl and benzyl; R2, R3 and A independently represent H or (C1-C8)alkoxy, wherein said alkyl is optionaly substituted by one or more -OH, (C1-C8)alkoxy, -NR7R8 or halogen; Q represents -(CH2)n-, where n = 1, 2, 3 or 4 or -(CH2)m-O-, where m = 2, 3 or 4; Z represents (C6-C14)aryl, (C1-C8)alkyl or (C3-C8)cycloalkyl; R4 and R5 each independently represent H, halogen, (C1-C8)alkyl, (C6-C14)aryl, (C6- C14)aryloxy, (C1-C8)alkoxy, (3-10 membered)heterocycloalkyl or (C3- C8)cycloalkoxy; wherein R4 and R5 are optionaly substituted by one or more - OH, (C1-C8)aIkoxy, -NR7R8 or halogen; Y represents -R6, -(CH2)o-R6, -C(R6)3 or -CH(R6)2, wherein 0 = 1, 2 or 3; R6 represents H, (C6-C14)aryl, (C1-10)alkyl, (C3-C10)cycloalkyl, (C5-C18)bicycloalkyl, (C5- C18)tricycloalkyl, (3-10 membered)heterocycloalkyl, (5-10 membered)heteroaryl, - C(=O)NR7R8, or -C(=O)OR7, wherein said R6 groups can optionaly be substituted with one or more X groups; wherein X = -OH, (C1-C8)aIkoxy, -NR11R12, -SO2R10, -C(=O)R10, halogen, cyano, (C1- C8)alkyl, (C1-C10)alkoxyalkyl, (5-10 membered)heteroaryl, (C6-C14)aryl, (C6- C14)aryloxy, benzyl, or (C1-C8)hydroxyalkyl; wherein R7 and R8 independently represent H, (C1-C8)alkyl, (C3-C8)cycloalkyl, (5-10 membered)heterocycloalkyl, (C1-C8)hydroxyalky, (5-10 membered)heteroaryl or (C1- C10)alkoxyalkyl; wherein R7 and R8 may optionaly be substituted by one or more X groups; or R7 and R8 together with the nitrogen in which they may be atached may form a (3- 10 membered)heterocycloalkyl group optionaly substituted by one or more X groups; wherein R10 represents (C1-C8)alkyl, (C3-C8)cycloalkyl, (3-10 membered)heterocycloalkyl, (C1-C8)hydroxyalky, (5-10 membered)heteroaryl or (C1- C10)alkoxyalkyl; wherein R11 and R12 independently represent H, (C1-C8)alkyl, (C3-C8)cycloalkyl, (5-10 membered)heterocycloalkyl, (C1-C8)hydroxyalky, (5-10 membered)heteroaryl or (C1- C10)alkoxyalkyl; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of PF-3463275, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula II, wherein: Z1 is selected from the group consisting of C1-4 alkyl, C3-6 Cycloalkyl, C1-4 alkoxy, C1-4 alkylthio, haloC1-4 alkyl, phenyl, haloC1-4 alkoxy, halophenyl, C1-4 alkylsulfoxy, C1-4 alkylsulfonyl, bromo and chloro; Z2 is selected from the group consisting of hydrogen, halogen, cyano, C1-4 alkyl, phenyl, haloC1-4 alkyl, haloC1-4 alkoxy, halophenyl, C1-4 alkoxyC1-4 alkyl and C3-6 cycloalkyl; Z3 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, C1-4alkoxy, C1-4 alkylthio, haloC1-4 alkyl, haloC1-4alkoxy, and C3-6 cycloalkyl; Z4 is selected from the group consisting of hydrogen, halogen, C1-3 alkyl, haloC1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, phenyl, haloC1-4 alkoxy, halophenyl, C1-4 alkoxyC1-4 alkyl and C3-6 cycloalkyl; Z5 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, iodo, hydroxy, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, phenyl, haloC1-4 alkyl, haloC1-4 alkoxy, halophenyl, C1-4 alkoxyC1-4 alkyl and C3-6 cycloalkyl; whereby if more than one of Z1 to Z5 is methoxy, then only Z1 and Z5 are methoxy R3 and R4 are independently selected from hydrogen and C1-4 alkyl, optionaly substituted with one or more groups Y; or R3 and R4 together with the nitrogen atom to which they are atached form a saturated or partialy unsaturated A-, 5- 6-or 7-membered carbocyclic ring optionaly substituted with a group Y'; Y is selected from the group consisting of C1-4 alkoxy, hydroxy, haloC1-4alkoxy and C3-5 cycloalkyl; Y' is selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, halogen, hydroxy, haloC1-4 alkoxy, C3-5 cycloalkyl and C5-10 aryl or Y' forms a -CH2- or -CH2-CH2- bridge between two atoms on the A-, 5-, 6- or 7-membered carbocyclic ring; R5 and R6 are independently C1-4 alkyl, optionaly substituted with one or more groups X; or R5 and R6 together with the carbon atom to which they are atached form a saturated 5- or 6-membered ring carbocyclic optionaly substituted with one or more groups X', in the case of R5 and R6 together with the carbon atom to which they are atached forming a 5- membered saturated carbocyclic ring, that ring may optionaly further comprising an additional heteroatom group selected from O, N and S(O)m; where m = 0, 1 or 2. X is selected from the group consisting of halogen, hydroxy, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy and C5-10 aryl; and X' is selected from the group consisting of halogen, hydroxy, C1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy and C5-10 aryl; whereby R3, R4, R5 and R6 are not al simultaneously unsubstituted methyl; with the provisos that when simultaneously Z1 is propyloxy, Z3 is chloro, Z2=Z4=Z5=H, and R5 and R6 are both methyl, then R3 and R4 together with the nitrogen atom to which they are atached do not form a 2-methylpyrrolidine group; when simultaneously Z1 is methyl, Z3 is methoxy, Z2=Z4=Z5=H, and R5 and R6 are both methyl, then R3 and R4 together with the nitrogen atom to which they are atached do not form a pyrolidine group; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of , or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula IV, Formula IV, wherein: Z is (CH2)n, O, S, SO, SO2 or N-R5; n is 0, 1 or 2; X represents 1-3 substituents independently selected from hydrogen, halogen, (C1-6) alkyloxy, (C3-6) cycloalkyloxy, (C6-12) aryloxy, (C6-12) aryl, thienyl, SR6, SOR6, SO2R6, NR6R6, NHR6, NH2, NHCOR6, NSO2R6, CN, COOR6 and (C1-4) alkyl, optionaly substituted with halogen, (C6-12) aryl, (C1-6) alkyloxy or (C6-12) aryloxy; or 2 substituents at adjacent positions together represent a fused (C5-6) aryl group, a fused (C5-6) cycloalkyl ring or O-(CH2)m-O; m is 1 or 2; Y represents 1-3 substituents independently selected from hydrogen, halogen, (C1-4) alkyloxy, SR6, NR6R6and (C1-4) alkyl, optionaly substituted with halogen; R1 is COOR7 or CONR8R9; R2 and R6 are (C1-4)alkyl; R3, R4 are R5 are independently hydrogen or (C1-4)alkyl; R7, R8 and R9are independently hydrogen, (C1-4)alkyl, (C6-12)aryl or arylalkyl; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of , ORG-25935, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula V, Formula V, wherein: n is an integer from 1 to 3; R1 and R2 are independently selected from hydrogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, cycloalkyl, or heterocyclyl wherein the aforementioned rings are optionaly substituted with Ra, Rb, or Rc independently selected from alkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, monosubstituted amino, or disubstituted amino; or R1 and R2, when atached to the same carbon atom, can combine to form cycloalkyl or monocyclic saturated heterocyclyl to give a spiro ring wherein the cycloalkyl or monocyclic saturated heterocyclyl can be optionaly substituted with Rd, Rc, or Rf independently selected from alkyl, alkoxy, fluoro, fluoroalkyl, fluoroalkoxy, hydroxy, monosubstituted amino, or disubstituted amino; or R1 and R2, when atached to carbon atoms 2 and 5 or 3 and 6 positions of the piperazine ring, can combine to form -C1-C3- alkylene chain wherein one of the carbon atoms in the alkylene chain is optionaly replaced by a -NR-, -O-, -S(O)n- (where R is hydrogen or alkyl and n is 0-2) and further wherein one or two hydrogen atoms in the alkylene chain can be optionaly substituted with one or two alkyl; R3, R4 and R5 are independently hydrogen, alkyl, fluoro, or fluoroalkyl; and Ar1 and Ar2 are independently aryl, heteroaryl, cycloalkyl, or heterocyclyl where each of the aforementioned ring is optionaly substituted with Rg, Rh or Ri where Rg is alkyl, - C=C- R6 (where R6 is aryl or heteroaryl), halo, haloalkyl, haloalkoxy, alkylthio, cyano, alkoxy, amino, monosubstituted amino, disubstituted amino, sulfonyl, acyl, carboxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, hydroxyalkoxy, alkoxyalkoxy, aminoalkoxy, aminosulfonyl, aminocarbonyl, or acylamino and Rh and Ri are independently selected from alkyl, halo, haloalkyl, haloalkoxy, alkylthio, cyano, alkoxy, amino, monosubstituted amino, disubstituted amino, sulfonyl, acyl, carboxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, hydroxyalkoxy, alkoxyalkoxy, aminoalkoxy, aminosulfonyl, aminocarbonyl, acylamino, aryl., heteroaryl, cycloalkyl, or heterocyclyl where the aromatic or alicyclic ring-in Rg, Rh and Ri is optionaly substituted with Rj, Rk, or Rl which are independently selected from alkyl, halo, haloalkyl, haloalkoxy, alkylthio, cyano, alkoxy, amino, monosubstituted amino, disubstituted amino, sulfonyl, acyl, carbpxy, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, hydroxyalkoxy, alkoxyalkoxy, aminoalkoxy, aminosulfonyl, aminocarbonyl, or acylamino; or a pharmaceuticaly acceptable salt thereof provided that: the compound of Formula V is not 2-(4-benzhydrylpiperazin-l-yl)acetic acid, 2-(4- ((4- chlorophenyl)(phenyl)methyl)piperazin-l-yl)acetic acid, 2-(2R,5S)-4-(R)-(4-(lH- tetrazol-5-yl)phenyl)(3-hydroxyphenyl)methyl)-2,5-dimethylpiperazin-l-yl)acetic acid, or 2- ((2R,5S)-4-((R)-(4-cyanophenyl)(3-hydroxyphenyl)methyl)-2,5- dimethylpiperazin-l-yl)acetic acid; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of , or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula VI, Formula VI, wherein: A represents a group of general formula N—R1, a group of general formula N+(O−)R1 or a group of general formula N+(R′)R1, and in which R1 represents either a hydrogen atom, or a linear or branched (C1–C7)alkyl group optionaly substituted with one or more fluorine atoms, or a (C4–C7)cycloalkyl group, or a (C3– C7)cycloalkyl(C1–C3)alkyl group, or a phenyl(C1–C3)alkyl group optionaly substituted with one or two hydroxyl or methoxy groups, or a (C2–C4)alkenyl group, or a (C2–C4)alkynyl group, R′ represents a linear or branched (C1–C7)alkyl group, X represents a hydrogen atom or one or more substituents chosen from halogen atoms and trifluoromethyl, linear or branched (C1–C4)alkyl and (C1–C4)alkoxy groups, R2 represents either a hydrogen atom, or one or more substituents chosen from halogen atoms and trifluoromethyl, (C1–C4)alkyl or (C1–C4)alkoxy groups, or amino groups of general formula NR3R4 in which R3 and R4 each represent, independently of each other, a hydrogen atom or a (C1–C4)alkyl group, or form with the nitrogen atom carying them a pyrolidine, piperidine or morpholine ring, or a phenyl group optionaly substituted with an atom or a group as defined for the symbol X above; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of , SSR-504734, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula VI, wherein: R1 is —(CH2)n—R, wherein n is independently 0-6, and Ra is selected from the group consisting of: C1-6 alkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxy, phenyl substituted with R2a, R2b and R2c, C3-6 cycloalyl, which is unsubstituted or substituted with C1-6 alkyl, 1-6 halogen, hydroxy or —NR10R11, —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxy or — NR10R11, —CO2R9, wherein R9 is independently selected from: hydrogen, —C1-6 alkyl, which is unsubstituted or substituted with 1-6 fluoro, benzyl, and phenyl, (6) —NR10R11, wherein R10 and R11 are independently selected from: hydrogen, —C1-6 alkyl, which is unsubstituted or substituted with hydroxy, 1-6 fluoro or —NR12R13, where R12 and R13 are independently selected from hydrogen and —C1-6 alkyl, —C3-6 cycloalkyl, which is unsubstituted or substituted with hydroxy, 1-6 fluoro or — NR12R13, benzyl, phenyl, and (7) —CONR10R11; R2 is selected from the group consisting of: phenyl, which is substituted with R2a, R2b and R2c, C1-8 alkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxy, —NR10R11, phenyl or heterocycle, where the phenyl or heterocycle is substituted with R2a, R2b and R2c, C3-6 cycloalkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxy or — NR10R11, and —C1-6alkyl-(C3-6cycloalkyl), which is unsubstituted or substituted with 1-6 halogen, hydroxy or —NR10R11; R2a, R2b and R2c are independently selected from the group consisting of: hydrogen, halogen, —C1-6 alkyl, which is unsubstituted or substituted with: 1-6 halogen, phenyl, C3-6cycloalkyl, or —NR10R11, —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxy, —SCF3, —SCHF2, —SCH3, —CO2R9, —CN, —SO2R9, —SO2—NR10R11, —NR10R11, —CONR10R11, and —NO2; R3 is selected from the group consisting of: C1-6alkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxyl, or —NR10R11, C3-6 cycloalkyl, which is unsubstituted or substituted with 1-6 halogen, hydroxyl or — NR10R11, R4 and R5 are independently selected from the group consisting of: hydrogen, and C1-6 alkyl, which is unsubstituted or substituted with halogen or hydroxyl, or R4 and R5 taken together form a C3-6 cycloalkyl ring; A is selected from the group consisting of: —O—, and —NR10—; m is zero or one, whereby when m is zero R2 is atached directly to the carbonyl; and pharmaceuticaly acceptable salts thereof and individual enantiomers and diastereomers thereof, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of , or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula VII, Formula VII, wherein: R1 is phenyl independently substituted from 1 to 5 times with halogen, C1-C3 alkyl, C3-C6cycloalkyl, OR9, or SR10, wherein C1-C3 alkyl and C3-C6cycloalkyl are optionaly substituted with 1 to 10 times with R7; R2 is H; R3 and R4 are each individualy H or CH3; R5 is selected from the group consisting of: hydrogen, C1-C6alkyl which is optionaly substituted from 1 to 11 times with R7, gem-dialkyl, and gem-dihalo; or two R5 substituents on the same carbon, together with the carbon atom to which they are atached, may form a 3-, 4-, or 5-membered cycloalkyl optionaly substituted from 1 to 10 times with R7; or two R5 substituents on adjacent carbons of the ring to which they are atached, together may form a 3-, 4-, 5- or 6-membered cycloalkyl optionaly substituted from 1 to 10 times with R7; R6 is wherein E, F, and G are each independently nitrogen or carbon and R6a is C1-C2 alkyl, which is optionaly substituted 1 to 5 times with halogen or deuterium; R7 is selected from the group consisting of: hydrogen, halogen, deuterium, gem-dialkyl, gem-dihalo, —OR9, —NR11R12, —NR11C(O)pR10, —S(O)pR10, —CN, —NO2, —C(O)pR10, — C(O)NR11R12, or —NR11C(S)R10, and oxo or thio; R8 is selected from the group consisting of: hydrogen, halogen, C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, C3-C7cycloalkyl, or C4-C7 cycloalkylalkyl, wherein each of the C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, C3-C7cycloalkyl, and C4- C7 cycloalkylalkyl is independently and optionaly substituted from 1 to 11 times with R7, or (4) —OR9, —NR11R12, —NR11C(O)pR10, —S(O)pR10, —CN, —NO2, —C(O)pR10, — C(O)NR11R12, or —NR11C(S)R10; R9 is selected from the group consisting of hydrogen, C1-C4 alkyl, C3-C7cycloalkyl, C4- C7 cycloalkylalkyl, —C(O)NR11R12, and —C(O)pR10, wherein each of C1-C4 alkyl, C3-C7cycloalkyl, and C4-C7 cycloalkylalkyl is optionaly substituted from 1 to 11 times with R7; R10 is selected from the group consisting of hydrogen, C1-C4 alkyl, C3-C7cycloalkyl C4- C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C4 alkyl, C3-C7cycloalkyl, and C4-C7 cycloalkylalkyl is optionaly substituted from 1 to 11 times with substituents as defined in R7 and aryl or heteroaryl is optionaly substituted from 1 to 10 times with R8; R11 and R12 are each independently selected from the group consisting hydrogen, C1-C4 alkyl, C3-C7cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C4 alkyl, C3-C7cycloalkyl, and C4-C7 cycloalkylalkyl is optionaly substituted from 1 to 11 times with substituents as defined in R7 and aryl or heteroaryl is optionaly substituted from 1 to 10 times with R8, or R11 and R12 are taken together with the nitrogen to which they are atached to form a saturated or partialy saturated monocyclic or fused bicyclic heterocycle optionaly substituted from 1 to 11 times with R7; A is X is N; Y is N; p is 1, or 2; and m is 0; with the folowing provisos that: R6 cannot be (a) 1H-1,2,3-triazol-4-yl, or (b) 5- methylisoxazol-4-yl; or an oxide thereof, a pharmaceuticaly acceptable salt of the compound or its oxide, or an individual enantiomer or diastereomer thereof. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is selected from any of the folowing

[0004] or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound having a formula of (ORG- 24598) or (LY-2365109), or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula IX, Formula IX, wherein: R1 represents phenyl or a 5 or 6 membered monocyclic heteroaryl having 1, 2, or 3 heteroatoms independently selected from O, N or S, wherein the phenyl or the heteroaryl is optionaly substituted with one or more R3; R2 represents aryl, a 5 or 6 membered monocyclic heteroaryl or a 8 to 10 membered bicyclic heteroaryl, the mono- or bicyclic heteroaryl having 1, 2, or 3 heteroatoms independently selected from O, N or S, wherein the aryl or the heteroaryl is optionaly substituted with one or more R4; R3 is a halogen, a C1-4-alkyl or a C3-6-cycloalkyl, wherein the C1-4-alkyl or the C3-6- cycloalkyl is optionaly substituted with one or more halogens; and R4 is a halogen, —CN, C1-4-alkyl, C3-6-cycloalkyl, —C1-3-alkyl —C3-6-cycloalkyl or — O—C1-6 alkyl, wherein the C1-4-alkyl, C3-6-cycloalkyl, —C1-3-alkyl —C3-6- cycloalkyl or the —O—C1-6-alkyl is optionaly substituted with one or more halogens; or a pharmaceuticaly acceptable salt thereof, or a tautomer or stereoisomer of the compound or its pharmaceuticaly acceptable salt, or a mixture of any of the foregoing. In certain embodiments, the compound of Formula IX can be represented by a compound of formula IX(a): Formula IX(a), or a pharmaceuticaly acceptable salt thereof, or a tautomer the compound or its pharmaceuticaly acceptable salt, or a mixture of any of the foregoing. In certain embodiments, the compound of Formula IX can be represented by a compound of formula IX(b): Formula IX(b), or a pharmaceuticaly acceptable salt thereof, or a tautomer the compound or its pharmaceuticaly acceptable salt, or a mixture of any of the foregoing. In certain embodiments, the compound of formula IX is a compound selected from any of the folowing, a stereoisomer or stereoisomeric mixture thereof, or a pharmaceuticaly acceptable salt thereof:

[0005]

[0006] . In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula X, Formula X, wherein: R1 is selected from the group consisting of 5 or 6 membered monocyclic heteroaryl, having 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of O, N and S(O)r, 5 or 6 membered monocyclic partialy saturated heterocycloalkyl, having 1, 2 or 3 heteroatoms independently selected from the group consisting of O, N and S(O)r, and 9 or 10 membered bicyclic heteroaryl, having 1, 2 or 3 heteroatoms independently selected from the group consisting of O, N and S(O)r, wherein r is 0, 1 or 2; wherein each of said groups a), b) and c) is optionaly substituted with 1 or more substituents independently selected from the group consisting of C1-4-alkyl-, C1-4- alkyl-O—, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, C3-6-cycloalkyl- and C3-6-cycloalkyl-O— and in case a substituent is atached to a nitrogen ring atom said substituent is selected from the group consisting of C1-4-alkyl-, C1-4-alkyl- CO—, C3-6-cycloalkyl- and C3-6-cycloalkyl-CO—, and wherein each of said C1-4-alkyl-, C1-4-alkyl-O—, C1-4-alkyl-CO—, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, C3-6-cycloalkyl-, C3-6-cycloalkyl-CO— or C3-6-cycloalkyl-O— substituents may be substituted by 1 or more substituents independently selected from the group consisting of fluoro, —CF3, —CHF2, — CH2F and —CN; R2 is selected from the group consisting of hydrogen, C1-4-alkyl-, C1-4-alkyl-O—, —CN and C3-6-cycloalkyl-, wherein each of said C1-4-alkyl-, C1-4-alkyl-O— and C3-6-cycloalkyl-group may be optionaly substituted with 1, 2, 3 or more substituents independently selected from the group consisting of fluoro, —CF3, —CHF2, —CH2F and —CN; R3 is selected from the group consisting of C1-6-alkyl-O—, C3-6-cycloalkyl-O—, morpholino, pyrazolyl and a 4 to 7 membered, monocyclic heterocycloalkyl-O— with 1 oxygen atom as ring member and optionaly 1 or 2 heteroatoms independently selected from the group consisting of O, N and S(O)s with s=0, 1 or 2, wherein said C1-6-alkyl-O— and said C3-6-cycloalkyl-O— may be optionaly substituted with 1, 2, 3 or more substituents independently selected from the group consisting of fluoro, —CF3, —CHF2, —CH2F, —CN, C1-4-alkyl-, C3-6-cycloalkyl-, C1-6- alkyl-O— and C3-6-cycloalkyl-O—; R4 is hydrogen; or R3 and R4 together with the ring atoms of the phenyl group to which they are bound may form a 4, 5 or 6 membered, monocyclic, partialy saturated heterocycloalkyl or a heteroaryl each of which having 1, 2 or 3 heteroatoms independently selected from the group consisting of O, N and S(O)s with s=0, 1 or 2, wherein there must be 1 ring oxygen atom that is directly atached to the ring carbon atom of said phenyl group to which R3 is atached to in general formula (I); wherein said heterocycloalkyl group may be optionaly substituted with 1, 2, 3 or more substituents independently selected from the group consisting of fluoro, —CF3, — CHF2, —CH2F, —CN, C1-4-alkyl-, C3-6-cycloalkyl-, C1-6-alkyl-O—, C3-6- cycloalkyl-O—, oxetanyl-O—, tetrahydrofuranyl-O— and tetrahydropyranyl-O— ; R5 is hydrogen; R6 is selected from the group consisting of hydrogen, C1-4-alkyl-SO2—, C3-6-cycloalkyl- SO2 and —CN; R7 is hydrogen; or one of the pairs a) R6 and R7 or b) R6 and R5 form together with the ring atoms of the phenyl group to which they are bound, a 5 or 6 membered, partialy saturated monocyclic heterocycloalkyl group having 1, 2 or 3 heteroatoms independently selected from the group consisting of O, N and S(O)uwith u=0, 1 or 2, wherein there must be 1 —SO2— member that is directly atached to the ring carbon atom of said phenyl group to which R6 is atached to in general formula (I), wherein said heterocycloalkyl group may be optionaly substituted with 1, 2, 3 or more substituents independently selected from the group consisting of fluoro, —CF3, — CHF2, —CH2F, —CN, C1-4-alkyl-, C1-6-alkyl-O— and C3-6-cycloalkyl-O— or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In certain embodiments, the compound of formula X is a compound selected from any of the folowing, a stereoisomer or stereoisomeric mixture thereof, or a pharmaceuticaly acceptable salt thereof:

[0007] , ,

[0008] , ,

[0009] For example, the compound of Formula X could be a diastereomeric mixture or single diasteromer of any of the folowing, or a pharmaceuticaly acceptable salt thereof:

[0010] , and . In certain embodiments, the compound of Formula X is a compound having a formula , or a pharmaceuticaly acceptable salt thereof. In some embodiments of the methods and uses disclosed herein, the GlyT1 inhibitor is a compound of Formula XI, Formula XI, wherein: R1 is halogen, —OR1′, —SR1″, cycloalkyl, cyclic amide, heterocycloalkyl, aryl or 5- or 6- membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen; R1′ and R1″ are each independently hydrogen, lower alkyl, lower alkyl substituted by halogen, —(CH2)x-cycloalkyl or —(CH2)x-aryl; R2 is —S(O)2-lower alkyl, —S(O)2NH-lower alkyl, NO2or CN; is an aromatic or partialy aromatic bicyclic amine, having one or two additional N-atoms selected from the group consisting of and wherein one of the additional N-ring atoms of the aromatic or partialy aromatic bicyclic amine can be available in form of its oxide ; R3 to R10 are each independently hydrogen, hydroxy, halogen, ═O, lower alkyl, cycloalkyl, heterocycloalkyl, lower alkoxy, CN, NO2, NH2, aryl, 5- or 6- membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen, —NH-lower alkyl, —N(lower alkyl)2, cyclic amide, —C(O)-cyclic amide, S-lower alkyl, —S(O)2-lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, lower alkyl substituted by hydroxy, —O—(CH2)y-lower alkoxy, — O(CH2)yC(O)N(lower alkyl)2, —C(O)-lower alkyl, —O—(CH2)x-aryl, —O— (CH2)x-cycloalkyl, —O—(CH2)x-heterocycloalkyl, —C(O)O-lower alkyl, — C(O)—NH-lower alkyl, —C(O)—N(lower alkyl)2, 2-oxy-5-aza- bicyclo[2.2.1]hept-5-yl or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; R, R′, R″ and R′″ are each independently hydrogen or lower alkyl; or R′ and R′″ in group e) together with —(CH2)4— form a six membered ring; and wherein al aryl-, cycloalkyl-, cyclic amide, heterocycloalkyl- or 5 or 6 membered heteroaryl groups as defined for R1, R1′, R1″ and R3 to R10 are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, ═O, halogen, lower alkyl, phenyl, lower alkyl substituted by halogen and lower alkoxy; n, m, o, p, q, r, s and t are each independently 1 or 2; x is 0, 1 or 2; and y is 1 or 2; or a pharmaceuticaly acceptable salt thereof. In certain embodiments, the compound of formula XI, or a pharmaceuticaly acceptable salt thereof, is a compound of Formula XI(a); , or a pharmaceuticaly acceptable salt thereof; a compound of Formula XI(b), , or a pharmaceuticaly acceptable salt thereof; a compound of Formula XI(c), , or a pharmaceuticaly acceptable salt thereof; a compound of Formula XI(d), , or a pharmaceuticaly acceptable salt thereof; a compound of Formula XI(e), , or a pharmaceuticaly acceptable salt thereof; a compound of Formula XI(f), , or a pharmaceuticaly acceptable salt thereof; a compound of Formula XI(g), , or a pharmaceuticaly acceptable salt thereof; or a compound of Formula XI(h), , or a pharmaceuticaly acceptable salt thereof. In certain embodiments, the compound of Formula XI is a compound selected from any of the folowing, a stereoisomer or stereoisomeric mixture thereof, or a pharmaceuticaly acceptable salt thereof:

[0011] , , , and . In certain of the methods and uses disclosed herein, the subject is a subject in need thereof. In some embodiments of the uses and methods as disclosed herein, the glycine transporter inhibitor, such as a GlyT1 inhibitor (e.g., a GlyT1 inhibitor as disclosed herein), or a pharmaceuticaly acceptable salt thereof, or a prodrug of the glycine transporter inhibitor, such as a GlyT1 inhibitor (e.g., a GlyT1 inhibitor as disclosed herein), or its pharmaceuticaly acceptable salt is administered in a therapeuticaly efective amount. In some embodiments, a compound, or a pharmaceuticaly acceptable salt, solvate or prodrug thereof, is chosen from a compound of as described herein. Any of the compounds provided for herein can be prepared as pharmaceuticaly acceptable salts, solvates or prodrugs and / or as part of a pharmaceutical composition as descripted in the cited patents or patent application publications herein. Although the compounds described herein may be shown with specific stereochemistries around certain atoms, such as cis or trans, the compounds can also be made in the opposite orientation or in a racemic mixture. Such isomers or racemic mixtures are encompassed by the present disclosure. Additionaly, although the compounds are shown colectively in a table, any compounds, or a pharmaceuticaly acceptable salt, solvate or prodrug thereof, can be chosen from the table and used in the embodiments provided for herein. The compounds described herein can be made according to the methods described in the cited patents or patent application publications herein. The compounds can be used to inhibit the GlyT1 transporter. Thus, in some embodiments, the compounds can be refered to as GlyT1 transporter inhibiting compounds or GlyT1 inhibitors. The compounds described herein can be administered in any conventional manner by any route where they are active. Administration can be systemic, topical, or oral. For example, administration can be, but is not limited to, parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal, oral, buccal, sublingual, or ocular routes, or intravaginal, by inhalation, by depot injections, or by implants. The mode of administration can depend on the conditions or disease to be targeted or treated. The selection of the specific route of administration can be selected or adjusted by the clinician according to methods known to the clinician to obtain the desired clinical response. In some embodiments, it may be desirable to administer one or more compounds, or a pharmaceuticaly acceptable salt, solvate or prodrug thereof, localy to an area in need of treatment. This may be achieved, for example, and not by way of limitation, by local infusion during surgery, topical application, e.g., in conjunction with a wound dressing after surgery, by injection, by means of a catheter, by means of a suppository, or by means of an implant, wherein the implant is of a porous, non-porous, or gelatinous material, including membranes, such as silastic membranes, or fibers. The compounds described herein can be administered either alone or in combination (concurrently or serialy) with other pharmaceuticals. For example, the compounds can be administered in combination with other drugs for the treatment of a MDS. Examples of other pharmaceuticals or medicaments are known to one of skil in the art and include but are not limited to those described herein. The means and methods for administration are known in the art and an artisan can refer to various pharmacologic references for guidance (see, for example, Modern Pharmaceutics, Banker & Rhodes, Marcel Dekker, Inc. (1979); and Goodman & Gilman’s The Pharmaceutical Basis of Therapeutics, 6th Edition, MacMilan Publishing Co., New York (1980). The amount of compound to be administered is that amount which is therapeuticaly efective. The dosage to be administered wil depend on the characteristics of the subject being treated, e.g., the particular animal treated, age, weight, health, types of concurrent treatment, if any, and frequency of treatments, and can be easily determined by one of skil in the art (e.g., by the clinician). The standard dosing for protamine can be used and adjusted (i.e., increased or decreased) depending upon the factors described above. The selection of the specific dose regimen can be selected or adjusted or titrated by the clinician according to methods known to the clinician to obtain the desired clinical response. The amount of a compound described herein that wil be efective in the treatment and / or prevention of a particular disease, condition, or disorder wil depend on the nature and extent of the disease, condition, or disorder, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays may optionaly be employed to help identify optimal dosage ranges. The precise dose to be employed in the compositions wil also depend on the route of administration, and the seriousness of the disorder, and should be decided according to the judgment of the practitioner and each patient’s circumstances. However, a suitable dosage range for oral administration is, generaly, from about 0.001 miligram to about 200 miligrams per kilogram body weight, from about 0.01 miligram to about 100 miligrams per kilogram body weight, from about 0.01 miligram to about 70 miligrams per kilogram body weight, from about 0.1 miligram to about 50 miligrams per kilogram body weight, from 0.5 miligram to about 20 miligrams per kilogram body weight, or from about 1 miligram to about 10 miligrams per kilogram body weight. In some embodiments, the oral dose is about 5 miligrams per kilogram body weight. In some embodiments, suitable dosage ranges for intravenous (i.v.) administration are from about 0.01 mg to about 500 mg per kg body weight, from about 0.1 mg to about 100 mg per kg body weight, from about 1 mg to about 50 mg per kg body weight, or from about 10 mg to about 35 mg per kg body weight. Suitable dosage ranges for other modes of administration can be calculated based on the forgoing dosages as known by those skiled in the art. For example, recommended dosages for intranasal, transmucosal, intradermal, intramuscular, intraperitoneal, subcutaneous, epidural, sublingual, intracerebral, intravaginal, transdermal administration or administration by inhalation are in the range of from about 0.001 mg to about 200 mg per kg of body weight, from about 0.01 mg to about 100 mg per kg of body weight, from about 0.1 mg to about 50 mg per kg of body weight, or from about 1 mg to about 20 mg per kg of body weight. Efective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. Such animal models and systems are wel known in the art. In certain embodiments, the glycine transporter inhibitor to be administered is a GlyT1 inhibitor, such as a GlyT1 inhibitor as disclosed herein. In some embodiments, suitable dosage ranges for the GlyT1 inhibitor are from about 5 mg / day to 200 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 5 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 10 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 15 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 20 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 25 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 30 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 35 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 40 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 45 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 50 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 55 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 60 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 65 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 70 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 75 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 80 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 85 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 90 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 95 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 100 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 105 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 110 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 115 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 120 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 125 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 130 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 135 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 140 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 145 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 150 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 155 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 160 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 165 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 170 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 175 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 180 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 185 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 190 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 195 mg / day. In some embodiments, the GlyT1 inhibitor is administered at 200 mg / day. In certain embodiments, the glycine transporter inhibitor to be administered is a GlyT1 inhibitor, such as bitopertin, pharmaceuticaly acceptable salt thereof, or a prodrug of bitopertin or its pharmaceuticaly acceptable salt. In some embodiments, the GlyT1 inhibitor is bitopertin. In some embodiments, suitable dosage ranges for bitopertin are from about 5 mg / day to 200 mg / day. In some embodiments, bitopertin is administered at 5 mg / day. In some embodiments, bitopertin is administered at 10 mg / day. In some embodiments, bitopertin is administered at 15 mg / day. In some embodiments, bitopertin is administered at 20 mg / day. In some embodiments, bitopertin is administered at 25 mg / day. In some embodiments, bitopertin is administered at 30 mg / day. In some embodiments, bitopertin is administered at 35 mg / day. In some embodiments, bitopertin is administered at 40 mg / day. In some embodiments, bitopertin is administered at 45 mg / day. In some embodiments, bitopertin is administered at 50 mg / day. In some embodiments, bitopertin is administered at 55 mg / day. In some embodiments, bitopertin is administered at 60 mg / day. In some embodiments, bitopertin is administered at 65 mg / day. In some embodiments, bitopertin is administered at 70 mg / day. In some embodiments, bitopertin is administered at 75 mg / day. In some embodiments, bitopertin is administered at 80 mg / day. In some embodiments, bitopertin is administered at 85 mg / day. In some embodiments, bitopertin is administered at 90 mg / day. In some embodiments, bitopertin is administered at 95 mg / day. In some embodiments, bitopertin is administered at 100 mg / day. In some embodiments, bitopertin is administered at 105 mg / day. In some embodiments, bitopertin is administered at 110 mg / day. In some embodiments, bitopertin is administered at 115 mg / day. In some embodiments, bitopertin is administered at 120 mg / day. In some embodiments, bitopertin is administered at 125 mg / day. In some embodiments, bitopertin is administered at 130 mg / day. In some embodiments, bitopertin is administered at 135 mg / day. In some embodiments, bitopertin is administered at 140 mg / day. In some embodiments, bitopertin is administered at 145 mg / day. In some embodiments, bitopertin is administered at 150 mg / day. In some embodiments, bitopertin is administered at 155 mg / day. In some embodiments, bitopertin is administered at 160 mg / day. In some embodiments, bitopertin is administered at 165 mg / day. In some embodiments, bitopertin is administered at 170 mg / day. In some embodiments, bitopertin is administered at 175 mg / day. In some embodiments, bitopertin is administered at 180 mg / day. In some embodiments, bitopertin is administered at 185 mg / day. In some embodiments, bitopertin is administered at 190 mg / day. In some embodiments, bitopertin is administered at 195 mg / day. In some embodiments, bitopertin is administered at 200 mg / day. The compounds described herein can be formulated for parenteral administration by injection, such as by bolus injection or continuous infusion. In some embodiments, the compounds can be administered by continuous infusion subcutaneously over a period of about 15 minutes to about 24 hours. Formulations for injection can be presented in unit dosage form, such as in ampoules or in multi-dose containers, with an optionaly added preservative. The compositions can take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and can contain formulatory agents such as suspending, stabilizing and / or dispersing agents. In some embodiments, the injectable is in the form of short-acting, depot, or implant and pelet forms injected subcutaneously or intramuscularly. In some embodiments, the parenteral dosage form is the form of a solution, suspension, emulsion, or dry powder. For oral administration, the compounds described herein can be formulated by combining the compounds with pharmaceuticaly acceptable cariers wel known in the art. Such cariers enable the compounds to be formulated as tablets, pils, dragees, capsules, emulsions, liquids, gels, syrups, caches, pelets, powders, granules, sluries, lozenges, aqueous or oily suspensions, for oral ingestion by a patient to be treated. Pharmaceutical preparations for oral use can be obtained by, for example, adding a solid excipient, optionaly grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients include, but are not limited to, filers such as sugars, including, but not limited to, lactose, sucrose, mannitol, and sorbitol; celulose preparations such as, but not limited to, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl celulose, hydroxypropylmethyl-celulose, sodium carboxymethylcelulose, and polyvinylpyrolidone (PVP). If desired, disintegrating agents can be added, such as, but not limited to, the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Oraly administered compositions can contain one or more optional agents, for example, sweetening agents such as fructose, aspartame or saccharin; flavoring agents such as peppermint, oil of wintergreen, or cherry; coloring agents; and preserving agents, to provide a pharmaceuticaly palatable preparation. Moreover, where in tablet or pil form, the compositions may be coated to delay disintegration and absorption in the gastrointestinal tract thereby providing a sustained action over an extended period of time. Selectively permeable membranes surrounding an osmoticaly active driving compound are also suitable for oraly administered compounds. Oral compositions can include standard vehicles such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, celulose, magnesium carbonate, etc. Such vehicles are suitably of pharmaceutical grade. Dragee cores can be provided with suitable coatings. For this purpose, concentrated sugar solutions can be used, which can optionaly contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestufs or pigments can be added to the tablets or dragee coatings for identification or to characterize diferent combinations of active compound doses. Pharmaceutical preparations which can be used oraly include, but are not limited to, push-fit capsules made of gelatin, as wel as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filer such as lactose, binders such as starches, and / or lubricants such as talc or magnesium stearate and, optionaly, stabilizers. In soft capsules, the active compounds can be dissolved or suspended in suitable liquids, such as faty oils, liquid parafin, or liquid polyethylene glycols. In addition, stabilizers can be added. For buccal administration, the compositions can take the form of, such as, tablets or lozenges formulated in a conventional manner. For administration by inhalation, the compounds described herein can be delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable propelant, such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit can be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, such as gelatin for use in an inhaler or insuflator can be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. The compounds described herein can also be formulated in rectal compositions such as suppositories or retention enemas, such as containing conventional suppository bases such as cocoa buter or other glycerides. The compounds described herein can also be formulated in vaginal compositions such as vaginal creams, suppositories, pessaries, vaginal rings, and intrauterine devices. In transdermal administration, the compounds can be applied to a plaster, or can be applied by transdermal, therapeutic systems that are consequently supplied to the organism. In some embodiments, the compounds are present in creams, solutions, powders, fluid emulsions, fluid suspensions, semi-solids, ointments, pastes, gels, jelies, and foams, or in patches containing any of the same. The compounds described herein can also be formulated as a depot preparation. Such long-acting formulations can be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Depot injections can be administered at about 1 to about 6 months or longer intervals. Thus, for example, the compounds can be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. In some embodiments, the compounds can be delivered in a controled release system. In one embodiment, a pump may be used (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng., 1987, 14, 201; Buchwald et al., Surgery, 1980, 88, 507 Saudek et al., N. Engl. J. Med., 1989, 321, 574). In some embodiments, polymeric materials can be used (see Medical Applications of Controled Release, Langer and Wise (eds.), CRC Pres., Boca Raton, Fla. (1974); Controled Drug Bioavailability, Drug Product Design and Performance, Smolen and Bal (eds.), Wiley, New York (1984); Ranger et al., J. Macromol. Sci. Rev. Macromol. Chem., 1983, 23, 61; see, also Levy et al., Science, 1985, 228, 190; During et al., Ann. Neurol., 1989, 25, 351; Howard et al., J. Neurosurg., 1989, 71, 105). In yet another embodiment, a controled-release system can be placed in proximity of the target of the compounds described herein, such as the liver, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controled Release, supra, vol.2, pp.115-138 (1984). Other controled- release systems discussed in the review by Langer, Science, 1990, 249, 1527-1533) may be used. It is also known in the art that the compounds can be contained in such formulations with pharmaceuticaly acceptable diluents, filers, disintegrants, binders, lubricants, surfactants, hydrophobic vehicles, water soluble vehicles, emulsifiers, bufers, humectants, moisturizers, solubilizers, and preservatives. The pharmaceutical compositions can also comprise suitable solid or gel phase cariers or excipients. Examples of such cariers or excipients include, but are not limited to, calcium carbonate, calcium phosphate, various sugars, starches, celulose derivatives, gelatin, and polymers such as polyethylene glycols. In some embodiments, the compounds described herein can be used with agents including, but not limited to, topical analgesics (e.g., lidocaine), barier devices (e.g., GelClair), or rinses (e.g., Caphosol). In some embodiments, the compounds described herein can be delivered in a vesicle, in particular a liposome (see, Langer, Science, 1990, 249, 1527-1533; Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein and Fidler (eds.), Liss, New York, pp.353-365 (1989); Lopez-Berestein, ibid., pp.317-327; see generaly ibid.). Suitable compositions include, but are not limited to, oral non-absorbed compositions. Suitable compositions also include, but are not limited to saline, water, cyclodextrin solutions, and bufered solutions of pH 3-9. The compounds described herein, or pharmaceuticaly acceptable salts, solvates or prodrugs thereof, can be formulated with numerous excipients including, but not limited to, purified water, propylene glycol, PEG 400, glycerin, DMA, ethanol, benzyl alcohol, citric acid / sodium citrate (pH3), citric acid / sodium citrate (pH5), tris(hydroxymethyl)amino methane HCl (pH7.0), 0.9% saline, and 1.2% saline, and any combination thereof. In some embodiments, excipient is chosen from propylene glycol, purified water, and glycerin. In some embodiments, the formulation can be lyophilized to a solid and reconstituted with, for example, water prior to use. When administered to a mammal (e.g., to an animal for veterinary use or to a human for clinical use) the compounds can be administered in isolated form. When administered to a human, the compounds can be sterile. Water is a suitable carier when the compound of Formula I-VII is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid cariers, particularly for injectable solutions. Suitable pharmaceutical cariers also include excipients such as starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, and ethanol. The present compositions, if desired, can also contain minor amounts of weting or emulsifying agents, or pH bufering agents. The compositions described herein can take the form of a solution, suspension, emulsion, tablet, pil, pelet, capsule, capsule containing a liquid, powder, sustained- release formulation, suppository, aerosol, spray, or any other form suitable for use. Examples of suitable pharmaceutical carriers are described in Remington’s Pharmaceutical Sciences, A.R. Gennaro (Editor) Mack Publishing Co. In some embodiments, the compounds are formulated in accordance with routine procedures as a pharmaceutical composition adapted for administration to humans. Typicaly, compounds are solutions in sterile isotonic aqueous buffer. Where necessary, the compositions can also include a solubilizing agent. Compositions for intravenous administration may optionaly include a local anesthetic such as lidocaine to ease pain at the site of the injection. Generaly, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermeticaly sealed container such as an ampoule or sachete indicating the quantity of active agent. Where the compound is to be administered by infusion, it can be dispensed, for example, with an infusion botle containing sterile pharmaceutical grade water or saline. Where the compound is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration. The pharmaceutical compositions can be in unit dosage form. In such form, the composition can be divided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of the preparations, for example, packeted tablets, capsules, and powders in vials or ampules. The unit dosage form can also be a capsule, cachet, or tablet itself, or it can be the appropriate number of any of these packaged forms. In some embodiments, a composition is in the form of a liquid wherein the active agent (i.e., one of the facialy amphiphilic polymers or oligomers disclosed herein) is present in solution, in suspension, as an emulsion, or as a solution / suspension. In some embodiments, the liquid composition is in the form of a gel. In other embodiments, the liquid composition is aqueous. In other embodiments, the composition is in the form of an ointment. In some embodiments, the composition is in the form of a solid article. For example, in some embodiments, the ophthalmic composition is a solid article that can be inserted in a suitable location in the eye, such as between the eye and eyelid or in the conjunctival sac, where it releases the active agent as described, for example, U.S. Pat. No.3,863,633; U.S. Pat. No.3,867,519; U.S. Pat. No.3,868,445; U.S. Pat. No. 3,960,150; U.S. Pat. No.3,963,025; U.S. Pat. No.4,186,184; U.S. Pat. No.4,303,637; U.S. Pat. No.5,443,505; and U.S. Pat. No.5,869,079. Release from such an article is usualy to the cornea, either via the lacrimal fluid that bathes the surface of the cornea, or directly to the cornea itself, with which the solid article is generaly in intimate contact. Solid articles suitable for implantation in the eye in such fashion are generaly composed primarily of polymers and can be bioerodible or non-bioerodible. Bioerodible polymers that can be used in the preparation of ocular implants carying one or more of compounds include, but are not limited to, aliphatic polyesters such as polymers and copolymers of poly(glycolide), poly(lactide), poly(epsilon-caprolactone), poly-(hydroxybutyrate) and poly(hydroxyvalerate), polyamino acids, polyorthoesters, polyanhydrides, aliphatic polycarbonates and polyether lactones. Suitable non-bioerodible polymers include silicone elastomers. The compositions described herein can contain preservatives. Suitable preservatives include, but are not limited to, mercury-containing substances such as phenylmercuric salts (e.g., phenylmercuric acetate, borate and nitrate) and thimerosal; stabilized chlorine dioxide; quaternary ammonium compounds such as benzalkonium chloride, cetyltrimethylammonium bromide and cetylpyridinium chloride; imidazolidinyl urea; parabens such as methylparaben, ethylparaben, propylparaben and butylparaben, and salts thereof; phenoxyethanol; chlorophenoxyethanol; phenoxypropanol; chlorobutanol; chlorocresol; phenylethyl alcohol; disodium EDTA; and sorbic acid and salts thereof. Optionaly one or more stabilizers can be included in the compositions to enhance chemical stability where required. Suitable stabilizers include, but are not limited to, chelating agents or complexing agents, such as, for example, the calcium complexing agent ethylene diamine tetraacetic acid (EDTA).For example, an appropriate amount of EDTA or a salt thereof, e.g., the disodium salt, can be included in the composition to complex excess calcium ions and prevent gel formation during storage. EDTA or a salt thereof can suitably be included in an amount of about 0.01% to about 0.5%. In those embodiments containing a preservative other than EDTA, the EDTA or a salt thereof, more particularly disodium EDTA, can be present in an amount of about 0.025% to about 0.1% by weight. One or more antioxidants can also be included in the compositions. Suitable antioxidants include, but are not limited to, ascorbic acid, sodium metabisulfite, sodium bisulfite, acetylcysteine, polyquaternium-1, benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, or other agents know to those of skil in the art. Such preservatives are typicaly employed at a level of from about 0.001% to about 1.0% by weight. In some embodiments, the compounds are solubilized at least in part by an acceptable solubilizing agent. Certain acceptable nonionic surfactants, for example polysorbate 80, can be useful as solubilizing agents, as can pharmaceuticaly acceptable glycols, polyglycols, e.g., polyethylene glycol 400 (PEG-400), and glycol ethers. Suitable solubilizing agents for solution and solution / suspension compositions are cyclodextrins. Suitable cyclodextrins can be chosen from α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, alkylcyclodextrins (e.g., methyl-β-cyclodextrin, dimethyl-β-cyclodextrin, diethyl-β-cyclodextrin), hydroxyalkylcyclodextrins (e.g., hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin), carboxy-alkylcyclodextrins (e.g., carboxymethyl-β- cyclodextrin), and sulfoalkylether cyclodextrins (e.g., sulfobutylether-β-cyclodextrin). In some embodiments, the composition optionaly contains a suspending agent. For example, in those embodiments in which the composition is an aqueous suspension or solution / suspension, the composition can contain one or more polymers as suspending agents. Useful polymers include, but are not limited to, water-soluble polymers such as celulosic polymers, for example, hydroxypropyl methylcelulose, and water-insoluble polymers such as cross-linked carboxyl-containing polymers. One or more acceptable pH adjusting agents and / or bufering agents can be included in the compositions, including acids such as acetic, boric, citric, lactic, phosphoric and hydrochloric acids; bases such as sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, sodium lactate and tris- hydroxymethylaminomethane; and buffers such as citrate / dextrose, sodium bicarbonate and ammonium chloride. Such acids, bases and bufers are included in an amount required to maintain pH of the composition in an acceptable range. One or more acceptable salts, solvates or prodrugs can be included in the compositions in an amount required to bring osmolality of the composition into an acceptable range. Such salts include, but are not limited to, those having sodium, potassium or ammonium cations and chloride, citrate, ascorbate, borate, phosphate, bicarbonate, sulfate, thiosulfate or bisulfite anions. In some embodiments, salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite and ammonium sulfate. In some embodiments, the salt is sodium chloride. Optionaly one or more acceptable surfactants, such as, but not limited to, nonionic surfactants, or co-solvents can be included in the compositions to enhance solubility of the components of the compositions or to impart physical stability, or for other purposes. Suitable nonionic surfactants include, but are not limited to, polyoxyethylene faty acid glycerides and vegetable oils, e.g., polyoxyethylene (60) hydrogenated castor oil; and polyoxyethylene alkylethers and alkylphenyl ethers, e.g., octoxynol 10, octoxynol 40; polysorbate 20, 60 and 80; polyoxyethylene / polyoxypropylene surfactants (e.g., Pluronic® F-68, F84 and P-103); cyclodextrin; or other agents known to those of skil in the art. Typicaly, such co- solvents or surfactants are employed in the compositions at a level of from about 0.01% to about 2% by weight. In some embodiments, pharmaceutical packs or kits comprising one or more containers filed with one or more compounds described herein are provided. Optionaly associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration for treating a condition, disease, or disorder described herein. In some embodiments, the kit contains more than one compound described herein. In some embodiments, the kit comprises a compound described herein in a single injectable dosage form, such as a single dose within an injectable device such as a syringe with a needle. In some embodiments, the methods comprise administering to the subject one or more compounds described herein or a pharmaceuticaly acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition of the same. In some embodiments, the subject is a subject in need of such treatment. As described herein, in some embodiments, the subject is a mammal, such as, but not limited to, a human. In some embodiments, also provided are one or more compounds described above, or a pharmaceuticaly acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising one or more compounds described above, for use in the manufacture of a medicament for the treatment of methods of treating and / or preventing MDS, or related syndrome thereof, including, but not limited to the conditions described herein, in a subject, such as those described herein. In some embodiments, the subject is a subject in need thereof. The present embodiments also provide the use of one or more compounds described above, or a pharmaceuticaly acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising one or more compounds described above, in the inhibition of a GlyT1 transporter, such as the presence on the surface of the cel. In some embodiments, the compounds, pharmaceuticaly acceptable salt thereof, or a pharmaceutical composition of the same inhibit the internalization, traficking, and / or degradation of the GlyT1 transporter. As used herein, “inhibition” can refer to inhibition of a specific activity. The activity of a GlyT1 transporter can be measured by any method known in the art including but not limited to the methods described herein. The compounds described herein are inhibitors of the GlyT1 transporter. The ability of the compounds to inhibit GlyT1 transporter activity may be measured using any assay known in the art. Generaly, assays for testing compounds that inhibit GlyT1 transporter activity include the determination of any parameter that is indirectly or directly under the influence of a GlyT1 transporter, e.g., a functional, physical, or chemical effect. Samples or assays comprising GlyT1 transporters that are treated with a potential inhibitor, are compared to control samples without the inhibitor to examine the extent of inhibition. Control samples (untreated with inhibitors) are assigned a relative GlyT1 transporter activity value of 100%. Inhibition of a GlyT1 transporter is achieved when the GlyT1 transporter activity value relative to the control is about 80%, 50%, or 25%. Ligand binding to a GlyT1 transporter can be tested in a number of formats. Binding can be performed in solution, in a bilayer membrane, atached to a solid phase, in a lipid monolayer, or in vesicles. For example, in an assay, the binding of the natural ligand to its transporter is measured in the presence of a candidate modulator, such as the compound described herein. Alternatively, the binding of the candidate modulator may be measured in the presence of the natural ligand. Often, competitive assays that measure the ability of a compound to compete with binding of the natural ligand to the transporter are used. Binding can be tested by measuring, e.g., changes in spectroscopic characteristics (e.g., fluorescence, absorbance, refractive index), hydrodynamic (e.g., shape) changes, or changes in chromatographic or solubility properties. After the transporter is expressed in cels, the cels can be grown in appropriate media in the appropriate cel plate. The cels can be plated, for example at 5000-10000 cels per wel in a 384 wel plate. In some embodiments, the cels are plated at about 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10000 cels / per wel. The plates can have any number of wels and the number of cels can be modified accordingly. Any medicament having utility in an application described herein can be used in co-therapy, co-administration or co-formulation with a composition as described above. Therefore, the compounds described herein can be administered either before, concurently with, or after such therapeutics are administered to a subject. The additional medicament can be administered in co-therapy (including co- formulation) with the one or more of the compounds described herein. In some embodiments, the response of the disease or disorder to the treatment is monitored and the treatment regimen is adjusted as necessary in light of such monitoring. Frequency of administration is typicaly such that the dosing interval, for example, the period of time between one dose and the next, during waking hours is from about 1 to about 24, about 2 to about 12 hours, from about 3 to about 8 hours, or from about 4 to about 6 hours. In some embodiments, the dose is administered 1, 2, 3, or 4 times a day. It wil be understood by those of skil in the art that an appropriate dosing interval is dependent to some degree on the length of time for which the selected composition is capable of maintaining a concentration of the compound(s) in the subject and / or in the target tissue (e.g., above the EC50 (the minimum concentration of the compound which inhibits the transporter’s activity by 90%). Idealy the concentration remains above the EC50 for at least 100% of the dosing interval. Where this is not achievable it is desired that the concentration should remain above the EC50 for at least about 60% of the dosing interval or should remain above the EC50 for at least about 40% of the dosing interval. Methods of Use The present disclosure provides methods of preventing or treating MDS, or symptoms and / or complications thereof, in a subject in need thereof, the method comprising administering to the subject one or more glycine transporter inhibitor or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more glycine transporter inhibitor or its pharmaceuticaly acceptable salt with the proviso the MDS is not MDS with isolated del(5q) chromosome. In certain embodiments, the glycine transporter inhibitor is a GlyT1 inhibitor, such as a GlyT1 inhibitor as disclosed herein. For example, the present disclosure provides a method of preventing, treating, or reducing the progression rate and / or severity of MDS in a subject, comprising administering to the subject bitopertin, , or a pharmaceuticaly acceptable salt thereof, or a prodrug of bitopertin or its pharmaceuticaly acceptable salt. In certain embodiments, bitopertin is not administered to a subject with MDS-RS. In embodiments, the present disclosure relates to methods of treating one or more symptoms or complications of a myelodysplastic syndrome (MDS) in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising one or more glycine transporter inhibitor (e.g., a GlyT1 inhibitor), or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more glycine transporter inhibitor (e.g., a GlyT1 inhibitor) or its salt. In certain embodiments, the disclosure relates to methods of preventing, treating, or reducing the progression rate and / or severity of one or more complications of MDS in a subject, the method comprising administering to the subject a pharmaceutical composition comprising one or more glycine transporter inhibitor (e.g., a GlyT1 inhibitor), or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more glycine transporter inhibitor (e.g., a GlyT1 inhibitor) or its salt. In embodiments, the MDS is LR-MDS (e.g., MDS with multilineage dysplasia (MDS-MLD) or MDS with single lineage dysplasia (MDS-SLD) or MDS with ring sideroblasts (MDS-RD such as those with the SF3B1 mutation). In some embodiments, the one or more GlyT1 inhibitor can be administered in conjunction with one or more curently available treatments. The terms "subject," an "individual," or a "patient" are interchangeable throughout the specification and refer to either a human or a non-human animal. These terms include mammals, such as humans, non-human primates, laboratory animals, livestock animals (including bovines, porcines, camels, etc.), companion animals (e.g., canines, felines, other domesticated animals, etc.) and rodents (e.g., mice and rats). In particular embodiments, the patient, subject or individual is a human. The present application provides methods of preventing, treating, or reducing the progression rate and / or severity of MDS, the method comprising administering to the subject one or more glycine transporter inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more glycine transporter inhibitor or its pharmaceuticaly acceptable salt. In some embodiments, the one or more glycine transporter inhibitor is one or more GlyT1 and / or GlyT2 inhibitors. In some embodiments, the one or more glycine transporter inhibitor is one or more GlyT1 inhibitors, such as one or more GlyT1 inhibitors as disclosed herein. In certain embodiments of the foregoing, the pharmaceutical composition further comprises a pharmaceuticaly acceptable carrier. For example, the present application provides a method of preventing, treating, or reducing the progression rate and / or severity of MDS in a subject, comprising administering to the subject a GlyT1 inhibitor such as bitopertin, or a pharmaceuticaly acceptable salt thereof, or a prodrug of bitopertin or its pharmaceuticaly acceptable salt. The present application further provides use of one or more glycine transporter inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more glycine transporter inhibitor or its pharmaceuticaly acceptable salt, in the manufacture of a formulation for the treatment of MDS in a subject. In some embodiments, the one or more glycine transporter inhibitor is one or more GlyT1 and / or GlyT2 inhibitors. In some embodiments, the one or more glycine transporter inhibitor is one or more GlyT1 inhibitor, such as one or more GlyT1 inhibitor as disclosed herein. In certain such embodiments, the GlyT1 inhibitor is bitopertin, or a pharmaceuticaly acceptable salt thereof, or a prodrug of bitopertin or its pharmaceuticaly acceptable salt. In certain embodiments of the foregoing, the formulation is administered in a therapeuticaly efective amount. Myelodysplastic syndrome (MDS) Myelodysplastic syndromes (MDS) are myeloid malignancies arising from bone marow (BM) hematopoietic stem cels (HSCs). MDS includes a heterogeneous group of clonal hematopoietic neoplasms. Over 50 diferent recurent somatic mutations have been identified in MDS, with over 90 % of patients carying at least one clonal somatic mutation. Defects associated with MDS include defective myeloid diferentiations, bone marow dysplasia, and inefective hematopoiesis resulting in peripheral blood cytopenias. Patients with MDS show increasing numbers of BM blasts over time, and 30% to 40% of cases progress to acute myeloid leukemia (AML). The World Health Organization (WHO) recognizes six main types of MDS as unclassifiable (MDS-U) or including: multilineage dysplasia (MDS-MLD), single lineage dysplasia (MDS-SLD), ring sideroblasts (MDS-RS), excess blasts (MDS-EB), and isolated del (MDS-5q). The survival statistics, based on patients diagnosed between 1982-2004, are typicaly classified into five diferent World Health Organization Prognostic Scoring system (WPSS) groups (very low, low, intermediate, high, and very high) having a median survival of 11.8, 5.5, 4, 2.2 years and 9 months, respectively. The risk of AML in each of the five groups is 3, 14, 33, 54, and 84%, respectively. This disclosure relates, in part, to treatment of anemia in very low-, low-risk, and intermediate-risk MDS (MDS-MLD and MDS-SLD), colectively refered to as low-risk MDS (“LR-MDS”), which is understood by those of ordinary skil in the art to be a relatively stable disease. Some patients also present with MDS-MLD or SLD that also exhibit ring sideroblasts (MDS-RS-SLD and MDS-RD-MLD, respectively) in the bone marrow (e.g., 5-14% RS in bone marow cels) as wel as expanded and inefective erythropoiesis (Nikpour, et al. Gene expression profiling of erythroblasts from refractory anaemia with ring sideroblasts (RARS) and efects of G-CSF. Br. J. Haematol.2010 Jun;149(6):844-54 (2010); Invernizzi, et al. Efects of mitochondrial feritin overexpression in normal and sideroblastic erythroid progenitors. Br. J. Haematol.2013 Jun;161(5):726-737; Malcovati, et al. Recent advances in the understanding of myelodysplastic syndromes with ring sideroblasts. Br. J. Haematol.2016 Sep;174(6):847-58). About two-thirds of al MDS patients wil present with lower-risk (LR-MDS) disease with minor clinical symptoms and mild cytopenias, with anemia being the most common symptom which occurs in almost 90% of such patients. This anemia is caused by inefective erythropoiesis and leads to increased proliferation of erythroid progenitor cels, increased disruption of abnormal erythroblasts and reduced diferentiation into RBCs. Erythropoiesis-stimulating agent (ESA) therapy often represents the first therapy for transfusion-dependent LR-MDS patients, with overal response rates of 20% to 40% and an 18- to 24-month duration of response. If no response occurs folowing ESA therapy, the patient is typicaly treated with luspateracept (MDS-RS (i.e., MDS with ring sideroblasts), Lenolidomide (MDS-5q), stem cel transplantation (if adverse risk factors are present), blood transfusion with iron chelation, or in various clinical trials (e.g., imetelstat, Roxadustat). With respect to iron chelation in the treatment of LR-MDS, these patients are prone to develop iron overload as a consequence of inefective erythropoiesis and chronic RBC transfusion therapy. Excessive accumulation of iron can lead to end-organ damage associated with secondary hemochromatosis. In a Phase 2 placebo-controled study investigating the iron chelator deferasirox (DFX) (iron chelation therapy (ICT) in LR- MDS patients with serum feritin > 1000 ng / mL and transfusion history of 15 to 75 packed red blood cel (PRBC) units, 225 patients were randomized, and iron chelation was associated with a 36.4% risk reduction in event-free survival (TELESTO trial (Novartis AG); MDS Event Free Survival with Iron Chelation Therapy Study, #NCT00940602; Angelucci, et al. Ann. Intern. Med.2020;172:513-522. doi:10.7326 / M19-0916;Caraway, et al. Hematology Am. Soc. Hematol. Educ. Program, (1): 426 (2020)). The trial compared deferasirox dispersible tablets (10 to 40 mg / kg per day (n=149) with a matching placebo (n=76). The primary endpoint was Event-Free Survival (EFS), defined as the time from the date of randomization to the first documented non-fatal even (related to cardiac or liver dysfunction and transformation to AML) or death, whichever occured first. The median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% Cl, 3.2 to 4.3 years] vs.3.0 years [Cl, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [Cl, 0.42 to 0.961). Adverse events occured in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure- adjusted incidence rates of adverse events (2' 15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarhea, 21.8 versus 18.7 for pyrexia, 16 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration. The protocol was amended from a Phase 3 to a Phase 2 study, with a reduced target sample size from 630 to 210 participants. There was diferential folow-up between treatment groups. The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinicaly manageable safety profile. Therefore, the study concluded, ICT may be considered in these patients.However, important limitations to highlight in the TELESTO trial include a long period of enrolment, a dramatic reduction in sample size, and a nonstandard definition of events. Published literature on iron chelation in MDS management is limited by retrospective or single institution studies, which have a lack of statistical power. Although chelation can be considered for lower-risk MDS patients with a high transfusion burden along with evidence of end-organ damage from iron deposition, it appears that its use should be deliberate and individualized. Givosiran (Givlaari ® (Alnylam Pharm.), an aminolevulinate synthase 1-directed smal interfering ribonucleic acid (siRNA) is also used to treat patients with acute MDSs by targeting and degrading ALAS1 mRNA in hepatocytes using RNA interference. The concerned risks associated with the use of givosiran include anaphylactic reactions, liver toxicity, and renal toxicity. For example, 15% patients in givosiran clinical trials showed transaminase (ALT) elevations 3 times the upper limit of normal. Additionaly, 15% of patients receiving givosiran have renal-related adverse reactions including elevated serum creatinine levels and decreased estimated glomerular filtration rate. Additional treatment pathways for MDS include treating isolated anemia, isolated thrombocytopenia, isolated neutropenia or multi-lineage cytopenia. For instance, asymptomatic low risk MDS can be monitored every one to three months until symptoms arise, isolated anemia may be treated by supportive transfusions and / or lenalidomide, isolated thrombocytopenia can be treated by supportive transfusions and / or a thrombopoietin agonist, isolated neutropenia can be treated with antivirals and / or antibacterials, and multi-lineage cytopenia can be treated with a hypomethylating agent or anti-thymocyte globulin (ATG). Thus, many treatments are being atempted for treating MDS but none have yet shown clear success. There is therefore a clear need in the art for identifying novel therapeutics that can be used for the treatment of LR-MDS, improved methods for treating LR-MDS, especialy the anemia associated therewith, in LR-MDS patients. The methods and use of glycine transporter inhibitors, such as, but not limited to, GlyT1 inhibitors, disclosed herein fulfil these needs as wel as others. Treatment of MDS In some embodiments, the disclosure provides methods of preventing or treating LR-MDS, or symptoms and / or conditions thereof, in a subject, the method comprising administering to the subject one or more glycine transporter inhibitor or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more glycine transporter inhibitor or its pharmaceuticaly acceptable salt. In certain embodiments, the glycine transporter inhibitor is a GlyT1 inhibitor, such as a GlyT1 inhibitor as disclosed herein. In exemplary embodiments, the GlyT1 inhibitor is bitopertin or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt. In some embodiments, the subject has or is at risk for developing MDS. In some embodiments, the MDS is low-risk MDS “LR-MDS” (e.g., MDS with multilineage dysplasia (MDS-MLD), MDS with single lineage dysplasia (MDS-SLD), and in certain embodiments MDS with ring sideroblasts (MDS-RD such as those with the SF3B1 mutation). In certain embodiments, the MDS is not MDS with isolated del(5q) chromosome. In certain embodiments, the subject treated in accordance with the methods described herein has LR-MDS and intact chromosome 5q. In some embodiments, the MDS is MDS-RD. In some embodiments, the MDS is LR-MDS without MDS-RS. In some embodiments, the one or more GlyT1 inhibitor can be administered in conjunction with one or more curently available treatments. In certain embodiments the MDS is classified as MDS-RS and the subject has one or more somatic mutations of the spliceosome selected from SF3B1, U2AF1, SRSF2 or ZRSR2. In certain embodiments, the MDS is classified as MDS-RS with single lineage dysplasia (MDS-RS-SLD) or MDS-RS with multilineage dysplasia (MDS-RS-MLD). In embodiments, the subject is classified with SF3B1-mutant MDS. In alternative embodiments, the MDS is other than SF3B1-mutant MDS. In embodiments, the methods of this disclosure further comprising screening for SF3B1 mutation in the subject. In certain embodiments, a subject treated in accordance with the methods provided herein has been diagnosed with IPSS-R defined MDS. IPSS-R refers to the International Prognostic Scoring System-Revised, which is utilized in the evaluation of prognosis in myelodysplastic syndromes. See, e.g., Greenberg et al., Blood, 2012; 120(12):2454-2465. The IPSS-R utilizes a criteria point system to characterize myelodysplastic syndrome patient outcomes as very low risk (0-1.5 risk score, median survival 8.8 years), low risk (1.5-3.0 risk score; median survival of 5.3 years), intermediate (3.0-4.5 point; median survival of 3.0 years); high risk (4.5-6.0 points; median survival of 1.6 years); or very high risk (risk score higher than 6; median survival of 0.8 years). The point system evaluates (i) the percentage of bone marow blasts in the subject; and (i) cytogenetics in the subject which defined as hemoglobin concentration (g / dL), absolute neutrophil count (×109 / L), and platelet count (×109 / L). In certain embodiments, the MDS is IPSS-defined very low risk MDS. In certain embodiments, the MDS is IPSS-R defined low risk MDS. In certain embodiments, the MDS is IPSS-R defined intermediate risk MDS. In certain embodiments, a subject treated in accordance with the methods provided herein has MDS-refractory cytopenia with multilineage dysplasia (MDS-RCMD). Provided herein are methods for treating one or more symptoms or complications of myelodysplastic syndrome (MDS) in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising one or more GlyT1 inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its pharmaceuticaly acceptable salt. In certain embodiments, the one or more symptoms or complications of MDS is selected from the group consisting of: edema, erythema, anemia, hypochromic anemia, hemolytic anemia, hemolysis, mild hemolysis, severe hemolysis, chronic hemolysis, inefective erythropoiesis, hemochromatosis, hemosiderosis, petechiae, dificulty breathing, recuring infections, hemorhage, thrombocytopenia, and acute myeloid leukemia (AML). Common, and serious, complications arising from cytopenia (low levels of red blood cels, white blood cels and / or platelets) include anemia, recurrent infections, and excess bleeding. Accordingly, subjects to be treated with methods of this disclosure may have below normal blood cel numbers of two or three of erythrocytes, leukocytes and thrombocytes. Other serious complications include an increased risk of cancer (e.g., AML). The methods of this disclosure treat and / or reduce the risk of these complications associated with MDS, especialy in subjects with MDS classified as LR-MDS. In embodiments, the subject to be treated has multi-lineage cytopenia, wherein the subject may have one or more of anemia, leukopenia or thrombocytopenia. In certain embodiments, the subject to be treated has isolated thrombocytopenia based on platelets <20K / L or <50K / L with bleeding. In embodiments, the subject is further receiving platelet transfusions and / or or growth factor treatment to help blood cels mature. In certain embodiments, a subject treated in accordance with the methods provided herein has a baseline platelet count less than 100×109 / L. In certain embodiments, a subject treated in accordance with the methods provided herein has a baseline platelet count between 100 to 400 ×109 / L. In certain embodiments, a subject treated in accordance with the methods provided herein has a baseline platelet count greater than 400×109 / L. In certain other embodiments, the subject to be treated has isolated neutropenia based on absolute neutrophil count <500. In embodiments, the subject is further receiving treatment for an infection. In certain embodiments, the treatment reduces the blood transfusion and / or platelet transfusion burden. In embodiments, the treatment increases neutrophil levels. In certain embodiments, the methods of this disclosure comprise administering to the subject in need thereof a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitors, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt as a treatment of cytopenia in the subject classified with LR-MDS. In this method, treating the complication of cytopenia and associated symptoms minimizes the transfusion burden for the subject. While supportive red blood cel (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, frequent transfusions are often complicated by iron overload and decreased quality of life; furthermore, patients either do not respond to ESAs or wil eventualy develop resistance. However, in certain embodiments, the subject is further receiving blood transfusions and / or growth factor treatment to help blood cels mature. In embodiments, the methods of this disclosure restrict iron reducing iron overload. In certain embodiments, the methods of this disclosure comprise administering to the subject in need thereof a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt as a treatment of anemia in the subject classified with LR-MDS. In embodiments, the anemia is aplastic anemia. In embodiments, the subject is transfusion dependent (>2 units / 8 weeks) and has isolated anemia (HGB<10g / dL). In embodiments, the subject’s heme levels are substantialy maintained during treatment. In alternative embodiments, the treatment decreases subject’s heme levels by no more than 10% (e.g., 10%, 15%, 20%, 25%, and 30%). In other alternative embodiments, the treatment increases hemoglobin levels. In certain embodiments, the treatment results in an increase in hemoglobin of > 1.5 g / dL for > two weeks or an increase in hemoglobin of > 1.5 g / dL for > eight weeks. In certain embodiments, the treatment increases red blood cel levels. In certain embodiments, hemoglobin levels in a subject treated in accordance with the methods provided herein are less than 10 g / dL, 9 g / dL, 8 g / dL, or 7 g / dL. In certain embodiments, hemoglobin levels in a subject treated in accordance with the methods provided herein are between 7 g / dL and 7.5 g / dL, between 7.5 g / dL and 8 g / dL, between 8 g / dL and 8.5 g / dL, between 8.5 g / dL and 9.0 g / dL, between 9.0 g / dL and 9.5 g / dL, or between 9.5 g / dL and 10.0 g / dL. In certain embodiments, a subject having anemia due to LR-MDS treated requires regular, lifelong red blood cel transfusions. In certain embodiments, a subject having anemia due to LR-MDS requires transfusion of 0 to 4 red blood cel units over a 8-weeks period. In certain embodiments, a subject having anemia due to LR- MDS requires transfusion of 4 to 6 red blood cel units over a 8-weeks period. In certain embodiments, a subject having anemia due to LR-MDS requires transfusion of less than 6 red blood cel units over a 8-weeks period. In certain embodiments, a subject having anemia due to LR- MDS requires transfusion of more than 6 red blood cel units over a 8-weeks period. In certain embodiments, a subject having anemia due to LR-MDS has a high transfusion burden. In certain embodiments, high transfusion burden is 12 or more red blood cel units over 24 weeks prior to treatment according to the methods provided herein. In certain embodiments, a subject treated in accordance with the methods provided herein has a low transfusion burden. In certain embodiments, the subject with a low transfusion burden treated in accordance with the methods provided herein requires at most 0, 1, 2, or 3 units of red blood cels per 8 weeks. In certain embodiments, a subject treated in accordance with the methods provided herein has a high transfusion burden. In certain embodiments, the subject with a high transfusion burden treated in accordance with the methods provided herein requires at least 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 units of red blood cels per 8 weeks. In certain embodiments, a subject treated in accordance with the methods provided herein has thrombocytopenia. In certain embodiments, a subject treated in accordance with the methods provided herein has less than 100×109 platelets per liter. In certain embodiments, a subject treated in accordance with the methods provided herein has 100 to 400×109 platelets per liter. In certain embodiments, a subject treated in accordance with the methods provided herein has more than 400×109 platelets per liter. In certain embodiments, a subject treated in accordance with the methods provided herein has neutropenia. In certain embodiments, a subject treated in accordance with the methods provided herein has an absolute neutrophil count of less than 1×109 per liter. In certain embodiments, a subject treated in accordance with the methods provided herein has less than 13,000 white blood cels per μL, less than 12,000 white blood cels per μL, less than 11,000 white blood cels per μL, less than 10,000 white blood cels per μL, less than 7,500 white blood cels per μL, or less than 500 white blood cels per μL. In certain embodiments, a subject treated in accordance with the methods provided herein has an EPO serum concentration of greater than 500 IU / L. In certain embodiments, a subject treated in accordance with the methods provided herein has an EPO serum concentration between 200 and 500 IU / L. In certain embodiments, a subject treated in accordance with the methods provided herein has an EPO serum concentration between 100 and 200 IU / L. In certain embodiments, a subject treated in accordance with the methods provided herein has an EPO serum concentration less than 100 IU / L. The presentation of MDS is heterogeneous, but patients often manifest with symptoms related to cytopenia such as fatigue, infections, or hemorhagic complications. A diagnostic evaluation of MDS in a patient with unexplained persistent cytopenia(s) curently requires a bone marow biopsy and aspiration to detect dysplasia and assess marow celularity. Moreover, cytogenetic testing is a standard of care in the context of workup and diagnosis of MDS. Accordingly, the subject to be treated with methods of this disclosure may have one of the folowing cytopenia assessments: A) i) anemia; and i) less than 5% of bone marow blood cels are blasts or immature blood cels; B) i) anemia; i) below normal erythrocyte numbers; and ii) more than 15% of those erythrocytes are sideroblasts; C) i) anemia; i) below normal blood cel numbers of at least two of erythrocytes, leukocytes and thrombocytes; and, ii) more than 15% of those erythrocytes are sideroblasts; D) i) anemia; i) below normal blood cel numbers of two or three of erythrocytes, leukocytes and thrombocytes; and, ii) between about 5% to 20 % of bone marow blood cels are immature blood cels or blasts; or E) : i) anemia; and i) less than 5% of blood or bone marow cels are immature blood cels or blasts. In certain embodiments, the methods of this disclosure comprise administering to the subject in need thereof a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitors, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt as a treatment of sideroblastic anemia in the subject classified with LR-MDS, wherein the anemia is sideroblastic anemia and the subject has at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% ring blasts as a percentage of bone marow erythroid precursors in subject’s bone marow. In certain embodiments, the percentage of erythroblasts in a subject treated in accordance with the methods provided herein that are ring sideroblasts is at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or at least 20%. In certain embodiments, the percentage of erythroblasts in a subject treated in accordance with the methods provided herein that are ring sideroblasts is at least 15%. In certain embodiments, the percentage of erythroblasts in a subject treated in accordance with the methods provided herein that are ring sideroblasts is about 15%. In certain embodiments, the percentage of erythroblasts in a subject treated in accordance with the methods provided herein that are ring sideroblasts is between about 15% and about 20%. In certain embodiments, the percentage of erythroblasts in a subject treated in accordance with the methods provided herein that are ring sideroblasts is between about 5% and 20%. In certain embodiments, a subject treated in accordance with the methods provided herein has a ringed sideroblast to normal erythroblast ratio of at least 1:20, at least 1:7, or at least 1:5. In certain embodiments, a subject treated has one or more mutations in the SF3B1 gene. In certain embodiments, the one or more mutations in SF3B1 gene has been confirmed by genetic analysis. In certain embodiments, the one or more mutations is in a non-coding region. In certain embodiments, SF3B1 is the gene encoding SF3B1. In certain embodiments, the one or more mutations is in a coding region. In certain embodiments, SF3B1 is SF3B1 protein. In certain embodiments, the one or more mutations in SF3B1 protein is selected from the group consisting of E622D, R625C, H662Q, H662D, K66N, K666T, K666Q, K666E, A672D, K700E, I704N. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation E622D. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation R625C. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation H662Q. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation H662D. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation K66N. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation K666T. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation K666Q. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation K666E. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation A672D. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 with the mutation K700E. In certain embodiments, a subject treated in accordance with the methods provided herein expresses SF3B1 protein with the mutation I704N. In a specific embodiment, a subject treated in accordance with the methods provided herein expresses SRSF2 with one or more mutations. In a specific embodiment, a subject treated in accordance with the methods provided herein expresses DNMT3A with one or more mutations. In a specific embodiment, a subject treated in accordance with the methods provided herein expresses TET2 with one or more mutations. In a specific embodiment, a subject treated in accordance with the methods provided herein expresses SETBP1 with one or more mutations. In certain embodiments, a subject treated in accordance with the methods provided herein has undergone prior treatment with one or more ESAs or is curently undergoing treatment with one or more ESAs. In certain embodiments, a subject treated in accordance with the methods provided herein does not respond to treatment with one or more ESAs. In certain embodiments, a subject treated in accordance with the methods provided herein is refractory to treatment with one or more ESAs. In certain embodiments, a subject treated in accordance with the methods provided herein becomes refractory to treatment with one or more ESAs. In certain embodiments, a subject treated in accordance with the methods provided herein is refractory to prior ESA treatment. In certain embodiments, a subject who is refractory to prior ESA treatment has documented non-response or is no longer responsive to prior ESA-containing regimen, either as single agent or combination with other agents (e.g., with G-CSF); the ESA regimen must have been either (a) recombinant human erythropoietin of greater than 40,000 IU / week for at least 8 doses or equivalent, or (b) darbepoetin alpha of greater than 500 ug once every three weeks for at least 4 doses or equivalent. In certain embodiments, a subject treated in accordance with the methods provided herein is intolerant to prior ESA-treatment. In certain embodiments, a subject who is intolerant to prior ESA-treatment has documented discontinuation of prior ESA-containing regimen, either as single agent or combination (e.g., with G-CSF), at any time after introduction due to intolerance or an adverse event. In certain embodiments, a subject treated in accordance with the methods provided herein is ESA-ineligible. In certain embodiments, a subject who is ESA-ineligible has a low chance of response to ESA based on an endogenous serum erythropoietin level of greater than 200 IU / L for subjects not previously treated with ESAs. In certain embodiments, the subject treated in accordance with the methods described herein can be of any age. In certain embodiments, the subject treated in accordance with the methods described herein is less than 18 years old. In a specific embodiment, the subject treated in accordance with the methods described herein is less than 13 years old. In another specific embodiment, the subject treated in accordance with the methods described herein is less than 12, less than 11, less than 10, less than 9, less than 8, less than 7, less than 6, or less than 5 years old. In another specific embodiment, the subject treated in accordance with the methods described herein is 1-3 years old, 3-5 years old, 5-7 years old, 7-9 years old, 9-11 years old, 11-13 years old, 13-15 years old, 15-20 years old, 20-25 years old, 25-30 years old, or greater than 30 years old. In another specific embodiment, the subject treated in accordance with the methods described herein is 30-35 years old, 35-40 years old, 40-45 years old, 45-50 years old, 50-55 years old, 55- 60 years old, or greater than 60 years old. In another specific embodiment, the subject treated in accordance with the methods described herein is 18-64 years old, 65-74 years old, or greater than 75 years old. Combination Therapy Optionaly, methods disclosed herein for preventing, treating, or reducing the progression rate and / or severity of one or more complications of a MDS in a subject, may further comprise administering to the patient one or more supportive therapies or additional active agents for treating LR-MDS. For example, the patient also may be administered one or more supportive therapies or active agents selected from the group consisting of: transfusion of red blood cels, granulocytes, and thrombocytes, an iron- chelating agent or multiple iron chelating agents (e.g., deferoxamine, deferiprone, and deferasirox), an EPO receptor activator (e.g., EPO, epoetin alfa, epoetin beta, epoetin delta, epoetin omega, darbepoetin alfa, methoxy-polyethelene-glycol epoetin beta, and synthetic erythropoiesis protein (SEP), a G-CSF analog, a GM-CSF analog, hepcidin or a hepcidin receptor activator, lenalidomide, thalidomide, pomalidomide, azacitidine, decitabine, antithymocyte globulin, and thrombomimetic agent, a histone deacetylase inhibitor, a p38MAPK inhibitor, a glutathione S-transferase π inhibitor, alemtuzumab, a DNA methyltransferase inhibitor, a histone deacetylase inhibitor, luspatercept, sotatercept, KER-050 and KER-047. In some embodiments, the subject is administered a combination treatment, e.g., a GlyT1 inhibitor as described herein, and one or more additional treatments known to be efective against MDS (e.g., azacytidine (VISAZA) or decitabine (DACOGEN), as described herein) or its associated symptoms. In one embodiment, a GlyT1 inhibitor as described herein is administered in combination with glucose or dextrose. For example, 10-20% dextrose in normal saline may be provided intravenously. Typicaly, when glucose is administered, at least 300 g of 10% glucose is administered intravenously daily. The GlyT1 inhibitor may also be administered intravenously, as part of the same infusion that is used to administer the glucose or dextrose, or as a separate infusion that is administered before, concurently, or after the administration of the glucose or dextrose. In some embodiments, the GlyT1 inhibitor is administered via a diferent route of administration (e.g., subcutaneously). In yet another embodiment, the GlyT1 inhibitor is administered in combination with total parenteral nutrition. The GlyT1 inhibitor may be administered before, concurent with, or after the administration of total parenteral nutrition. In certain embodiments, a GlyT1 inhibitor is administered in combination with one or more additional treatments, e.g., another treatment known to be efective in treating MDS or symptoms of MDS. In one embodiment, the GlyT1 inhibitor is administered in combination with a heme product (e.g., hemin, heme arginate, or heme albumin). In a further embodiment, the GlyT1 inhibitor is administered in combination with a heme product and glucose, a heme product and dextrose, or a heme product and total parenteral nutrition. The additional treatment(s) may be administered before, after, or concurrent with the administration of GlyT1 inhibitor. The GlyT1 inhibitor and an additional therapeutic agent can be administered in combination in the same composition, e.g., intravenously, or the additional therapeutic agent can be administered as part of a separate composition or by another method described herein. In some embodiments, the subject has previously been treated with a heme product (e.g., hemin, heme arginate, or heme albumin), as described herein. In some embodiments, administration of the GlyT1 inhibitor, or administration of the GlyT1 inhibitor in combination one or more additional treatments (e.g., iron-chelating agents, EPO receptor activator, or the like). In some such embodiments, the GlyT1 inhibitor is administered according to a regular dosing regimen, e.g., b.i.d., daily, weekly, biweekly, or monthly. EXEMPLIFICATION The invention now being generaly described, it wil be more readily understood by reference to the folowing examples, which are included merely for purposes of ilustration of certain embodiments of the present invention, and are not intended to limit the invention. Example 1: Synthesis of Compounds The compounds disclosed herein can be made in accordance with wel-known procedures and by processes known and disclosed in the art. For example, compounds of Formula I, such as bitopertin, can be prepared in accordance with the synthetic protocols provided in U.S. Patent Nos.7,319,099, 9,877,963, and 7,812,161, the contents of which are hereby incorporated by reference in their entirety. In addition, compounds of Formula I, such as PF-3463275, can be prepared in accordance with the synthetic protocols provided in U.S. Patent No.8,124,639, the contents of which are hereby incorporated by reference in its entirety. Example 2: Bitopertin efects on inefective erythropoiesis in a mouse model of myelodysplastic syndrome (MDS) MDS is a heterogenous group of clonal myeloid neoplasms which are characterized by ineffective erythropoiesis and cytopenia, most commonly anemia. As such, heme restriction by bitopertin may enhance erythropoiesis and improve anemia in MDS patients. To test this hypothesis, a wel-established mouse model of MDS, the NUP98:HOXD13 fusion transgenic mice (Lin et al, Blood 2005; 106:287-295) wil be assessed folowing administration of bitopertin. Starting at 5-months of age, the MDS mice are fed with a control diet or a diet containing bitopertin at 100 or 200 parts per milion (ppm) ad libitum for 8 weeks. Both diets contain 50 ppm iron, which is considered a suficient or replete amount. At the end of the 8-week feeding regimen, hematological parameters of the bitopertin treated mice are compared to that of mice treated with the control diet. Assessment of bitopertin’s ability to reverse inefective erythropoiesis, increase hemoglobin and thus improve anemia in the MDS mice wil be determined. INCORPORATION BY REFERENCE Al publications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specificaly and individualy indicated to be incorporated by reference. While specific embodiments of the subject mater have been discussed, the above specification is ilustrative and not restrictive. Many variations wil become apparent to those skiled in the art upon review of this specification and the claims below. The ful scope of the invention should be determined by reference to the claims, along with their ful scope of equivalents, and the specification, along with such variations.

Claims

CLAIMS We claim:

1. A method of treating a myelodysplastic syndrome (MDS) in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt with the proviso the MDS is not MDS with isolated del(5q) chromosome.

2. A method of treating one or more symptoms or complications of a myelodysplastic syndrome (MDS) in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising one or more GlyT1 inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its pharmaceuticaly acceptable salt.

3. The method of claim 2, wherein the one or more symptoms or complications of MDS is selected from the group consisting of: edema, erythema, anemia, hypochromic anemia, hemolytic anemia, hemolysis, mild hemolysis, severe hemolysis, chronic hemolysis, ineffective erythropoiesis, hemochromatosis, hemosiderosis, petechiae, dificulty breathing, recuring infections, hemorrhage, thrombocytopenia, and acute myeloid leukemia (AML).

4. The method of any one of claims 1-3, wherein the MDS is selected from the group consisting of: i) MDS with multilineage dysplasia (MDS-MLD), i) MDS with single lineage dysplasia (MDS-SLD), ii) MDS with ring sideroblasts (MDS-RS), iv) MDS with excess blasts (MDS-EB), and v) unclassifiable MDS.

5. The method of any one of claim 1-4, wherein the subject is classified based on the World Health Organization Prognostic Scoring system (WPSS) as very low, low or intermediate.

6. The method of claim 5, wherein the MDS is selected from the group consisting of: i) MDS with multilineage dysplasia (MDS-MLD), or i) MDS with single lineage dysplasia (MDS-SLD).

7. The method of claim 5, wherein the subject is classified as lower-risk MDS (LR-MDS).

8. The method of any one of claim 5-7, wherein the administering to the subject a pharmaceutical composition comprising one or more glycine transporter 1 (GlyT1) inhibitor, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the one or more GlyT1 inhibitor or its salt is a treatment of anemia in the subject classified with LR-MDS.

9. The method of any one of claims 1-8, wherein the subject is transfusion dependent (>2 units / 8 weeks) and has isolated anemia (HGB<10g / dL).

10. The method of any one of claims 1-8, wherein the subject has isolated thrombocytopenia based on platelets <20K / L or <50K / L with bleeding.

11. The method of any one of claims 1-8, wherein the subject has isolated neutropenia based on absolute neutrophil count <500.

12. The method of any one of claims 1-8, wherein the subject has multi- lineage cytopenia.

13. The method of claim 12, wherein the subject has anemia.

14. The method of claim 12, wherein the subject has leukopenia.

15. The method of claim 12, wherein the subject has thrombocytopenia.

16. The method of claim 8, wherein the treatment restricts iron reducing iron overload.

17. The method of any one of claim 1-4, wherein the MDS is MDS-RS and the subject has one or more somatic mutations of the spliceosome selected from SF3B1, U2AF1, SRSF2 or ZRSR2.

18. The method of claim 17, wherein the MDS is MDS-RS with single lineage dysplasia (MDS-RS-SLD) or MDS-RS with multilineage dysplasia (MDS- RS-MLD).

19. The method of claims 17 or 18, wherein the subject is classified with SF3B1-mutant MDS.

20. The method of claim 19 wherein the one or more GlyT1 inhibitor is not bitopertin.

21. The method of any one of claims 1-18, wherein the MDS is other than SF3B1-mutant MDS.

22. The method of any one of claim 1-21, further comprising screening for SF3B1 mutation in the subject.

23. The method of any preceding claim, wherein the GlyT1 inhibitor demonstrates an EC50 of less than 500 nM.

24. The method of any preceding claim, wherein the GlyT1 inhibitor demonstrates an EC50 of less than 100 nM.

25. The method of any one of claims 1-24, wherein the subject’s heme levels are substantialy maintained during treatment.

26. The method of any one of claims 1-24, wherein the treatment decreases subject’s heme levels by no more than 10% (e.g., 10%, 15%, 20%, 25%, and 30%).

27. The method of any one of claims 1-24, wherein the dosage of the pharmaceutical composition does not cause a substantial reduction in heme levels.

28. The method of any one of claims 1-27, wherein the subject has: i) anemia; and i) less than 5% of bone marow blood cels are blasts or immature blood cels.

29. The method of any one of claims 1-27, wherein the subject has: i) anemia; i) below normal erythrocyte numbers; and ii) more than 15% of those erythrocytes are sideroblasts.

30. The method of any one of claims 1-27, wherein the subject has: i) anemia; i) below normal blood cel numbers of at least two of erythrocytes, leukocytes and thrombocytes; and, ii) more than 15% of those erythrocytes are sideroblasts.

31. The method of any one of claims 1-27, wherein the subject has: i) anemia; i) below normal blood cel numbers of two or three of erythrocytes, leukocytes and thrombocytes; and, ii) between about 5% to 20 % of bone marow blood cels are immature blood cels or blasts.

32. The method of any one of claims 1-27, wherein the subject has: i) anemia; and i) less than 5% of blood or bone marrow cels are immature blood cels or blasts.

33. The method of any one of claims 1-27, wherein the subject has below normal blood cel numbers of two or three of erythrocytes, leukocytes and thrombocytes.

34. The method of any one of claim 1-33 wherein the subject is further receiving blood transfusions and / or growth factor treatment to help blood cels mature.

35. The method of any one of claim 1-34, wherein the subject is further receiving platelet transfusions and / or or growth factor treatment to help blood cels mature.

36. The method of any one of claims 1-35, wherein the subject is further receiving treatment for an infection.

37. The method of any one of claims 1-36, wherein the treatment reduces the blood transfusion and / or platelet transfusion burden.

38. The method of any one of claims 1-37, wherein the GlyT1 inhibitor is a compound having a formula of Formula I, wherein: Ar is unsubstituted or substituted aryl or 6-membered heteroaryl containing one, two or three nitrogen atoms, wherein the substituted aryl and the substituted heteroaryl groups are substituted by one or more substituents selected from the group consisting of hydroxy, halogen, NO2, CN, (C1-C6)-alkyl, (C1-C6)-alkyl substituted by halogen, (C1-C6)-alkyl substituted by hydroxy, (CH2)n—(C1-C6)-alkoxy, (C1- C6)-alkoxy substituted by halogen, NR7R8, C(O)R9, SO2R10, and — C(CH3)═NOR7, or are substituted by a 5-membered aromatic heterocycle containing 1-4 heteroatoms selected from N and O, which is optionaly substituted by (C1-C6)-alkyl; R1 is hydrogen or (C1-C6)-alkyl; R2 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkenyl, (C1-C6)-alkyl substituted by halogen, (C1-C6)-alkyl substituted by hydroxy, (CH2)n—(C3-C7)-cycloalkyl optionaly substituted by (C1-C6)-alkoxy or by halogen, CH(CH3)—(C3-C7)-cycloalkyl, (CH2)n+1—C(O)—R9, (CH2)n+1—CN, bicyclo[2.2.1]heptyl, (CH2)n+1—O—(C1- C6)-alkyl, (CH2)n-heterocycloalkyl, (CH2)n-aryl or (CH2)n-5 or 6-memberedheteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur or nitrogen wherein aryl, heterocycloalkyl and heteroaryl are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, halogen, (C1-C6)-alkyl and (C1-C6)-alkoxy; R3, R4 and R6 are each independently hydrogen, hydroxy, halogen, (C1-C6)-alkyl, (C1- C6)-alkoxy or O—(C3-C6)-cycloalkyl; R5 is NO2, CN, C(O)R9 or SO2R10; R7 and R8 are each independently hydrogen or (C1-C6)-alkyl; R9 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8; R10 is (C1-C6)-alkyl optionaly substituted by halogen, (CH2)n—(C3-C6)-cycloalkyl, (CH2)n—(C3-C6)-alkoxy, (CH2)n-heterocycloalkyl or NR7R8; n is 0, 1, or 2; or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt.

39. The method of claim 38, wherein the GlyT1 inhibitor is a compound having a formula of, bitopertin, or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt.

40. The method of any one of claims 1-39, wherein the pharmaceutical composition further comprises a pharmaceuticaly acceptable carier.

41. The method of any one of claims 1-40, wherein the GlyT1 inhibitor, or pharmaceuticaly acceptable salt thereof, or prodrug of the GlyT1 inhibitor or itspharmaceuticaly acceptable salt, is administered in a therapeuticaly effective amount.

42. The method of any one of claims 1-41, wherein the myelodysplastic syndrome is untreated.

43. The method of any one of claims 1-42, wherein the GlyT1 inhibitor, or pharmaceuticaly acceptable salt thereof, or prodrug of the GlyT1 inhibitor or its pharmaceuticaly acceptable salt is administered as a first line treatment for MDS.

44. The method of any one of claims 1-42, wherein the GlyT1 inhibitor, or pharmaceuticaly acceptable salt thereof, or prodrug of the GlyT1 inhibitor or its pharmaceuticaly acceptable salt is administered as a second line, third line, or fourth line of treatment for the myelodysplastic syndrome.

45. The method of any one of claims 1-44, wherein the myelodysplastic syndrome is subsequent to acute myeloid leukemia.

46. The method of any one preceding claim, wherein the treatment increases red blood cel levels.

47. The method of any one preceding claim, wherein the treatment increases hemoglobin levels.

48. The method of claim 47, wherein the treatment results in an increase in hemoglobin of > 1.5 g / dL for > two weeks.

49. The method of claim 48, wherein the treatment results in an increase in hemoglobin of > 1.5 g / dL for > eight weeks.

50. The method of any one preceding claim, wherein the subject has been administered one or more blood cel transfusions prior to the start of treatment.

51. The method of any one preceding claim, wherein the subject is a low transfusion burden patient.

52. The method of any one of claims 1-51, wherein the patient is a high transfusion burden patient.

53. The method any one of claims 50-52, wherein the treatment decreases blood cel transfusion burden.

54. The method of claim 53, wherein the treatment decreases blood cel transfusion by > 50% for at least four weeks relative to the equal time prior to start of treatment.

55. The method of claim 53, wherein the treatment decreases blood cel transfusion by > 50% for at least eight weeks relative to the equal time prior to start of treatment.

56. The method of any one preceding claim, wherein the patient has an International Prognostic Scoring System (IPSS) or IPSS-R score of low or intermediate.

57. The method of any one of claims 13, or 28-32, wherein the anemia is sideroblastic anemia and the subject has at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% ring blasts as a percentage of bone marow erythroid precursors in subject’s bone marrow.

58. The method of any one of claims 1-57, wherein the treatment increases neutrophil levels.

59. The method of any one of claims 1-58, wherein the GlyT1 inhibitor is bitopertin or a pharmaceuticaly acceptable salt thereof, or a prodrug of the compound or its pharmaceuticaly acceptable salt.

60. The method of any one of claims 1-59, wherein the method further comprises administering one or more supportive therapy for sideroblastic anemia.

61. The method of claim 60, wherein the supportive therapy is transfusion of one or more of: red blood cels, granulocytes, and thrombocytes.

62. The method of any one of claims 60 or 61, wherein the supportive therapy comprises administration of an iron-chelating agent or multiple iron-chelating agents.

63. The method of claim 62, wherein the iron-chelating agent or multiple iron-chelating agents are selected from: a) deferoxamine; b) deferiprone; and c) deferasirox.

64. The method of any one of claims 60-63, wherein the supportive therapy comprises administering an EPO receptor activator.

65. The method of claim 64, wherein the EPO receptor activator is selected from: EPO, epoetin alfa, epoetin beta, epoetin delta, epoetin omega, darbepoetin alfa, methoxy- polyethylene-glycol epoetin beta, and synthetic erythropoiesis protein (SEP).

66. The method of any one of claims 60-65, wherein the supportive therapy comprises administration of one or more agents selected from the group consisting of: a G-CSF analog, a GM-CSF analog, an iron-chelating agent, hepcidin or a hepcidin receptor activator, lenalidomide, thalidomide, pomalidomide, azacitidine, decitabine, antithymocyte globulin, and thrombomimetic agent, a histone deacetylase inhibitor, a p38MAPK inhibitor, a glutathione S-transferase π inhibitor, alemtuzumab, a DNA methyltransferase inhibitor, and a histone deacetylase inhibitor.

67. The method of any one of claims 60-66, wherein the supportive therapy comprises administration of one or more agents selected from the group consisting of luspatercept, sotatercept, KER-050 and KER-047.

68. The method of any one of claim 1-67, wherein the treatment decreases iron overload.

69. The method of any one of claims 1-68, wherein the treatment decreases iron content in the liver and / or spleen.

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