75747-14-7 Usage
Description
Telatinib is a small molecule tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor-2 (VEGFR-2) and the platelet-derived growth factor receptor-β (PDGFR-β). It is designed to inhibit the growth of tumor blood vessels and reduce the proliferation of tumor cells.
Used in Oncology:
Telatinib is used as an anti-angiogenic agent for the treatment of various types of cancer. It works by inhibiting the activity of VEGFR-2 and PDGFR-β, which are key drivers of tumor angiogenesis and growth. This leads to a reduction in the formation of new blood vessels that supply nutrients and oxygen to the tumor, ultimately inhibiting tumor growth and progression.
Used in Drug Combination Therapy:
Telatinib is also used in combination with other cancer therapies, such as chemotherapy and targeted agents, to enhance the overall treatment efficacy. The combination of Telatinib with other drugs can help overcome drug resistance, improve patient outcomes, and provide a more comprehensive approach to cancer treatment.
Used in Clinical Trials:
Telatinib is currently being evaluated in various clinical trials for its potential use in treating different types of cancer, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and renal cell carcinoma (RCC). These trials aim to determine the safety, tolerability, and efficacy of Telatinib in combination with other cancer therapies, as well as to identify the optimal dosing regimens and patient populations that may benefit the most from this treatment approach.
Targets
HSP90 5 nM.
In vitro
17-AAG, an analog of geldanamycin, exhibits greater than 100 times higher binding affinity for Hsp90 derived from HER-2-overexpressing cancer cells (BT474, N87, SKOV3 and SKBR3) or BT474 breast carcinoma cells with IC50 values of 5-6 nM. 17-AAG causes the degradation of HER2, HER3, Akt, and both mutant and wild-type androgen receptor (AR), leading to the RB-dependent G1 growth arrest of prostate cancer cells such as LNCaP, LAPC-4, DU-145, and PC-3 with IC50 values of 25-45 nM. [2] In addition to inducing apoptosis of Ba/F3 cells transformed with wild-type BCR-ABL with an IC50 of 5.2 μM, 17-AAG has the ability to induce apoptosis of cells transformed with imatinib mesylate-resistant T315I and E255K BCR-ABL mutants with IC50 values of 2.3 μM and 1.0 μM, respectively, by inducing the degradation of both wild-type BCR-ABL protein and mutants.
Biological Activity
Inhibitor of heat shock protein 90 (Hsp90) chaperone activity, and an analog of geldanamycin (9,13-Dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione, 9-carbamate ). Subsequently inhibits the activity of oncogenic proteins such as p185 erbB-2 (IC 50 = 31 nM), N-ras, Ki-ras and c-Akt. Antitumor in vivo .
Biochem/physiol Actions
17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone and is an analog of geldanamycin.
References
1) Schulte et al. (1998), The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin; Cancer Chemother. Pharmacol. 42 273
2) Kamal et al. (2003), A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors; Nature, (b>425 407
3) Kaur et al. (2004), Therapeutic and diagnostic implications of Hsp90 activation; Clinical Cancer Res. 10 4813
Check Digit Verification of cas no
The CAS Registry Mumber 75747-14-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,5,7,4 and 7 respectively; the second part has 2 digits, 1 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 75747-14:
(7*7)+(6*5)+(5*7)+(4*4)+(3*7)+(2*1)+(1*4)=157
157 % 10 = 7
So 75747-14-7 is a valid CAS Registry Number.
InChI:InChI=1/C31H43N3O8/c1-8-12-33-26-21-13-17(2)14-25(41-7)27(36)19(4)15-20(5)29(42-31(32)39)24(40-6)11-9-10-18(3)30(38)34-22(28(21)37)16-23(26)35/h8-11,15-17,19,24-25,27,29,33,36H,1,12-14H2,2-7H3,(H2,32,39)(H,34,38)/b11-9+,18-10-,20-15+/t17-,19+,24+,25+,27-,29+/m1/s1
75747-14-7Relevant articles and documents
MICELLE ENCAPSULATION OF THERAPEUTIC AGENTS
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Paragraph 0091, (2016/11/17)
The invention provides active agents, such as paclitaxel, rapamycin, or 17-DMAG, encapsulated by safe poly(ethylene glycol)-block-poly(lactic acid) (“PEG-b-PLA”) micelles. The compositions provide effective solubilization of drug combinations, such as paclitaxel, rapamycin, and 17-DMAG, as well as others described herein. A significant advantage of PEG-b-PLA as a carrier is that it is less toxic than Cremophor EL or DMSO, which are used in currently known compositions. Additionally, PEG-b-PLA micelles are easier to handle than DMSO and they do not possess a foul odor, which is a problem with formulations currently in clinical trials. Accordingly, the invention provides stable and biocompatible drug formulations that improve bioavailability without causing toxicity. It was also found that larger doses of individual drugs in micelle formulations can be administered compared to non-micelle formulations.
Geldanamycin derivatives and neuroprotective effect on cultured P19-derived neurons
Tadtong, Sarin,Meksuriyen, Duangdeun,Tanasupawat, Somboon,Isobe, Minoru,Suwanborirux, Khanit
, p. 2939 - 2943 (2008/02/04)
Geldanamycin (1), an antifungal and anticancer ansamycin, was reported as a neurotrophic and neuroprotective substance against antineoplastic drugs, paclitaxel, vincristine, and cisplatin, on cultured dorsal root ganglion neurons from chick embryos. In this study, 1 in a large quantity, together with a known 17-O-demethylgeldanamycin (2), and a new 17-O-demethylgeldanamycin hydroquinone (3) were obtained from a mangrove Streptomyces sp. A series of O-alkyl and N-alkyl derivatives of 1 were prepared by modification of C-17 and/or C-19 on the quinone ring and were evaluated for in vitro activity against P19-derived neurons. Compound 1 and 19-O-methylgeldanamycin (7) at a very low dose (1 nM) enhanced survival and neurite outgrowth of P19-derived neurons and prevented neurotoxicity of paclitaxel and vinblastine. Compound 7, possessing the lowest cytotoxicity and neurotoxicity, is serving as the most promising candidate in neurodegenerative therapy against neurotoxic anticancer drugs.
Oral pharmaceutical formulations and methods for producing and using same
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Page/Page column 14, (2008/06/13)
Oral pharmaceutical formulations and methods of producing and using the same are described and claimed. The formulations are dispersions of phospholipids and one or more pharmacologically active compounds, In preferred embodiments, the pharmaceutically active compounds are ansamycins, pharmaceutically acceptable salts, or prodrugs thereof.