47 results about "Receptor selectivity" patented technology

This invention is directed to methods for treating conditions which present with low bone mass in a patient in need thereof using continuous combination therapy with a synergistically effective combination of an EP₄ receptor selective agonist or a pharmaceutically acceptable salt thereof, such as 5-(3-{2S-[3R-hydroxy-4-(3-trifluoromethyl-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-thiophene-2-carboxylic acid or a pharmaceutically acceptable salt thereof; and an estrogen or a pharmaceutically effective salt thereof, The present methods are useful for treating conditions that present with low bone mass including osteoporosis, osteotomy, osteoporotic fracture, childhood idiopathic bone loss, periodontitis and low bone mass and for enhancing bone healing following facial reconstruction, maxillary reconstruction or mandibular reconstruction, inducing vertebral synostosis, enhancing long bone extension, enhancing the healing rate of a bone graft or a long bone fracture or enhancing prosthetic ingrowth in a patient in need thereof.

Human receptor selective atrial natriuretic factor variants containing various substitutions, especially G16R, show equal potency and binding affinity for the human A-receptor but have decreased affinity for the human clearance or C-receptor. These ANF variants have natriuretic, diuretic and vasorelaxant activity but have increased metabolic stability, making them suitable for treating congestive heart failure, acute kidney failure and renal hypertension.

An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

Analogs of SRIF which are selective for SSTR4 in contrast to the other cloned SRIF receptors are useful in determining tissue and cellular expression of the receptor SSTR4 and its biological role in regulating tumor growth. SRIF analog peptides, such as des-AA^{1,2,4,5,12,13}[Ala⁷]-SRIF; des-AA^{1,2,4,5,12,13}[Aph⁷]-SRIF, des-AA^{1,2,4,5,12,13}[Aph⁷]Cbm-SRIF; des-AA^{1,2,4,5,12,13}[Tyr²,Ala⁷]-Cbm-SRIF, and des-AA^{1,2,4,5,12,13}[Tyr⁷,C^βMe-L-2Nal⁸]-SRIF, and counterparts incorporating D-Cys³ and/or D-Trp⁸ and/or Ala¹¹, bind with high affinity to the cloned human receptor SSTR4 and activate the receptor, but they do not bind with significant affinity to human SSTR1, SSTR2, SSTR3 or SSTR5. By incorporating an iodinated tyrosine in position-2 in these SSTR4-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, cytotoxins or highly radioactive elements can be N-terminally coupled or complexed thereto.

The present invention relates generally to receptor-selective variants of the low-density lipoprotein receptor-associated protein (RAP) and compositions thereof, methods of generating such variants and methods of using such receptor-selective RAP variant compositions for therapeutic purposes. The invention also relates to antibodies that bind to one or a small subset of CR-containing proteins.

The present invention relates to a compound medicine for external application for curing psoriasis. It is characterized by that in the matrix carrier of said compound medicine for external application are contained the following effective active components: (wt%) tazarotenje 0.025-0.1% and cortical hormone 0.01-0.2%. Its therapeutic effect is good, and it has no adverse reaction.

A method of post-stroke treatment at delayed timepoints with sigma receptor agonists. Sigma receptors are promising targets for neuroprotection following ischemia. One of the key components in the demise of neurons following ischemic injury is the disruption of intracellular calcium homeostasis. The sigma receptor agonist, DTG, was shown to depress [Ca²⁺]_i elevations observed in response to ischemia induced by sodium azide and glucose deprivation. Two sigma receptor antagonists, metaphit and BD-1047, were shown to blunt the ability of DTG to inhibit ischemia-evoked increases in [Ca²⁺]_i. DTG inhibition of ischemia-induced increases in [Ca²⁺]_i was mimicked by the sigma-1 receptor-selective agonists, carbetapentane, (+)-pentazocine and PRE-084, but not by the sigma-2 selective agonist, ibogaine, showing that activation of sigma-1 receptors is responsible for the effects. Activation of sigma receptors can ameliorate [Ca²⁺]_i dysregulation associated with ischemia in cortical neurons, providing neuroprotective properties. The effects of 1,3-di-o-tolyguanidine (DTG), a high affinity sigma receptor agonist, as a potential treatment for decreasing infarct area at delayed time points was further examined in rats. DTG treatment significantly reduced infarct area in both cortical/striatal and cortical/hippocampal regions by >80%, relative to control rats. These findings were confirmed by immunohistochemical experiments using the neuronal marker, mouse anti-neuronal nuclei monoclonal antibody (NeuN), which showed that application of DTG significantly increased the number of viable neurons in these regions. Furthermore, DTG blocked the inflammatory response evoked by MCAO, as indicated by decreases in the number of reactive astrocytes and activated microglia/macrophages detected by immunostaining for glial fibrillary acidic protein (GFAP) and binding of isolectin IB4, respectively. Thus, the sigma receptor-selective agonist, DTG, can enhance neuronal survival when administered 24 hr after an ischemic stroke. In addition, the efficacy of sigma receptors for stroke treatment at delayed time points is likely the result of combined neuroprotective and anti-inflammatory properties of these receptors.

The invention provides retinoic acid receptor (RAR) selective agonists and formulations thereof for the treatment of disease or for inducing a medically beneficial effect.

The present invention discloses a piperazine (piperidine) cyclohexyl derivative and applications of the piperazine (piperidine) cyclohexyl derivative in treatment of neuropsychiatric diseases. According to the present invention, the pharmacological experiment results show that the piperazine (piperidine) cyclohexyl derivative provides high affinity with a dopamine D2 receptor, a dopamine D3 receptor, a serotonin 5-HT1A receptor and a serotonin 5-HT2A receptor, provides good D3/D2 receptor selectivity and good 5-HT1A/5-HT2A receptor selectivity, and provides low affinity with alpha receptor; the in vivo test results show that the preferred compound has characteristics of good anti-schizophrenia effect, good pharmacokinetic property, low side effect, low acute toxicity and high safety, and has the development value of being adopted as the novel efficient and low-toxic anti-neuropsychiatric disease; and the piperazine (piperidine) cyclohexyl derivative is a compound represented by the structural general formula (I), or a geometric isomer, an optical isomer, a salt, a hydrate or a solvate thereof. The formula (I) is defined in the specification.

The invention relates to beta-galactosidase with broadened nucleoside substrate specificity. An amino acid sequence of the beta-galactosidase with the broadened nucleoside substrate specificity is shown as SEQ ID No. 1 (sequence identifier number 1). The invention further provides a gene for encoding the beta-galactosidase with the broadened nucleoside substrate specificity. The beta-galactosidase with the broadened nucleoside substrate specificity has new receptor selectivity, can conduct transglycosylation on a phenolic compound which is difficult to glycosylate or cannot be glycosylated by the natural beta-galactosidase, can serve as a powerful tool to modify the phenolic compound and relevant drug molecules, and has a wide application prospect.

This invention discloses some receptor-selective lymphotoxin (LT) mutants and the ratio, the ability of these lymphotoxin mutants combining with the human TNFRI to that with the human TNFRII, is more than 10. The preparation method and the use of the above said LT mutants are also disclosed. In this invention, the LT mutants bind to the TNFRI selectively and that decreases the binding to the TNFRII in a large range, thereby the toxic effect which may be caused by the TNFRII will be reduced.

The invention discloses a novel thiazole derivative or salt, an isomer, a preparation method and application thereof. A compound shown as a formula (I) has a Sigma 1 receptor antagonism effect, and has strong in vitro affinity to sigma 1R in the aspect of in vitro receptor affinity. Meanwhile, in D2L radioactive ligand binding analysis and 5HT-1A receptor, CB1 receptor and CB2 receptor cAMP tests,the affinity to the receptors is poor, and high receptor selectivity is shown. Mouse acetic acid twisting tests show that the compound has an analgesic effect. Through rat oral administration pharmacokinetic experiments, it can be known that the compound is long in half-life period, low in clearance rate and large in AUClast; Cmax can be quickly reached after oral administration, and the compoundis extremely quick to absorb and suitable for medicine.

Provided are methods and compositions directed towards the treatment of an individual having cancer by providing adoptive cell transfer therapy and administering to the individual a long acting IL-2Ralpha beta-biased agonist.

The invention relates to a dopamine D2 receptor selective agonist and application thereof. Specifically, the invention discloses an agonist with selectivity to DRD2 and discloses a potential application value of the agonist in disease treatment. The invention discloses an agonist with DRD2 selectivity for the first time, and the specific targeting DRD2 of the agonist can play a role in treating low dopamine related diseases such as Parkinson's disease, attention deficit hyperactivity disorder, pituitary adenoma, hyperprolactinemia, hyperactivity leg syndrome, negative schizophrenia and the like while side effects are reduced to the maximum extent.

The invention relates to a mesenchymal stem cell exosome-AM1241 complex and an application of the mesenchymal stem cell exosome-AM1241 complex in treatment of Alzheimer's disease. It is found for the first time that the exosome-loaded CB2 receptor selective agonist AM1241 can effectively improve the Alzheimer's disease, and animal experiments show that an Exo-AM1241 nano-drug system can basically recover the learning and memory ability of an Alzheimer's disease model mouse to a normal level; it is found for the first time that AM1241 can effectively improve the Alzheimer's disease; the invention also proves that the improvement effect of the mesenchymal stem cell exosome-AM1241 complex on the Alzheimer's disease is obviously better than that of the single AM1241 or exosome, and reveals that the effects and molecular mechanisms of the mesenchymal stem cell exosome-AM1241 complex, the single AM1241 or exosome on improving the Alzheimer's disease are obviously different.