WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205635
CAS#: 1186231-83-3
Description: TAK-441 is a potent inhibitor of Hedgehog (Hh) signaling pathway, TAK-441 is also a novel pyrrolo[3,2-c]quinoline-4-one derivative, which chemical structure is shown as the following. TAK-441 showed activity to suppress transcription factor Gli1 mRNA expression in tumor-associated stromal tissue and inhibited tumor growth (treatment/control ratio, 3%) in a mouse medulloblastoma allograft model owing to the improved PK profile based on increased solubility. TAK-441 is currently in clinical trials for the treatment of advanced solid tumors.
MedKoo Cat#: 205635
Name: TAK-441
CAS#: 1186231-83-3
Chemical Formula: C28H31F3N4O6
Exact Mass: 576.21957
Molecular Weight: 576.56
Elemental Analysis: C, 58.33; H, 5.42; F, 9.89; N, 9.72; O, 16.65
Synonym: TAK441, TAK441, TAK 441
IUPAC/Chemical Name: 6-Ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
InChi Key: ZADWXQMNNVICKB-UHFFFAOYSA-N
InChi Code: InChI=1S/C28H31F3N4O6/c1-3-19-13-20-23(27(40)35(19)14-21(37)17-7-5-4-6-8-17)25(41-16-28(29,30)31)24(33(20)2)26(39)32-18-9-11-34(12-10-18)22(38)15-36/h4-8,13,18,36H,3,9-12,14-16H2,1-2H3,(H,32,39)
SMILES Code: O=C(C(N1C)=C(OCC(F)(F)F)C2=C1C=C(CC)N(CC(C3=CC=CC=C3)=O)C2=O)NC4CCN(C(CO)=O)CC4
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 576.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Goldman J, Eckhardt SG, Borad MJ, Curtis KK, Hidalgo M, Calvo E, Ryan DP, Wirth LJ, Parikh A, Partyka J, Faessel H, Gangolli E, Stewart S, Rosen LS, Bowles DW. Phase 1 Dose-Escalation Trial of the Oral Investigational Hedgehog Signaling Pathway Inhibitor TAK-441 in Patients with Advanced Solid Tumors. Clin Cancer Res. 2014 Dec 12. pii: clincanres.1234.2014. [Epub ahead of print] PubMed PMID: 25501576.
2: Williams R. Discontinued in 2013: oncology drugs. Expert Opin Investig Drugs. 2015 Jan;24(1):95-110. Epub 2014 Oct 14. PubMed PMID: 25315907.
3: Ishii T, Shimizu Y, Nakashima K, Kondo S, Ogawa K, Sasaki S, Matsui H. Inhibition mechanism exploration of investigational drug TAK-441 as inhibitor against Vismodegib-resistant Smoothened mutant. Eur J Pharmacol. 2014 Jan 15;723:305-13. doi: 10.1016/j.ejphar.2013.11.014. Epub 2013 Nov 28. PubMed PMID: 24291104.
4: Sandhiya S, Melvin G, Kumar SS, Dkhar SA. The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628. PubMed PMID: 23662017; PubMed Central PMCID: PMC3643342.
5: Ibuki N, Ghaffari M, Pandey M, Iu I, Fazli L, Kashiwagi M, Tojo H, Nakanishi O, Gleave ME, Cox ME. TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling. Int J Cancer. 2013 Oct 15;133(8):1955-66. doi: 10.1002/ijc.28193. Epub 2013 May 6. PubMed PMID: 23564295.
6: Kogame A, Tagawa Y, Shibata S, Tojo H, Miyamoto M, Tohyama K, Kondo T, Prakash S, Shyu WC, Asahi S. Pharmacokinetic and pharmacodynamic modeling of hedgehog inhibitor TAK-441 for the inhibition of Gli1 messenger RNA expression and antitumor efficacy in xenografted tumor model mice. Drug Metab Dispos. 2013 Apr;41(4):727-34. doi: 10.1124/dmd.112.049650. Epub 2013 Jan 8. PubMed PMID: 23298863.
7: Ohashi T, Oguro Y, Tanaka T, Shiokawa Z, Tanaka Y, Shibata S, Sato Y, Yamakawa H, Hattori H, Yamamoto Y, Kondo S, Miyamoto M, Nishihara M, Ishimura Y, Tojo H, Baba A, Sasaki S. Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: modification of the core skeleton for improved solubility. Bioorg Med Chem. 2012 Sep 15;20(18):5507-17. doi: 10.1016/j.bmc.2012.07.034. Epub 2012 Jul 27. PubMed PMID: 22898254.
8: Tang JY, Marghoob AA. Emerging treatments and signaling pathway inhibitors. Semin Cutan Med Surg. 2011 Dec;30(4 Suppl):S14-8. doi: 10.1016/j.sder.2011.11.002. Review. PubMed PMID: 22177102.
