A83-01


Catalog No. size PriceQuantity
M6893-2 2mg solid $162
M6893-10 10mg solid $636

Description

Cas:909910-43-6

Product Information

A-83-01 is an ALK inhibibitor. It was found that A-83-01 inhibited the transcriptional activity induced by TGF-beta type I receptor ALK-5 and that by activin type IB receptor ALK-4 and nodal type I receptor ALK-7, the kinase domains of which are structurally highly related to those of ALK-5. A-83-01 was found to be more potent in the inhibition of ALK5 than a previously described ALK-5 inhibitor, SB-431542, and also to prevent phosphorylation of Smad2/3 and the growth inhibition induced by TGF-beta. A-83-01 inhibited the epithelial-to-mesenchymal transition induced by TGF-beta, suggesting that A-83-01 and related molecules may be useful for preventing the progression of advanced cancers.

 

Chemical Formula: C25H19N5S

 

Exact Mass: 421.13612

 

Molecular Weight: 421.52

 

Elemental Analysis: C, 71.23; H, 4.54; N, 16.61; S, 7.61

 

Chemical Name: 3-(6-methylpyridin-2-yl)-N-phenyl-4-(quinolin-4-yl)-1H-pyrazole-1-carbothioamide

 

InChi Key:

HIJMSZGHKQPPJS-UHFFFAOYSA-N

 

InChi Code: InChI=1S/C25H19N5S/c1-17-8-7-13-23(27-17)24-21(19-14-15-26-22-12-6-5-11-20(19)22)16-30(29-24)25(31)28-18-9-3-2-4-10-18/h2-16H,1H3,(H,28,31)

 

Smiles Code:

S=C(N1N=C(C2=NC(C)=CC=C2)C(C3=CC=NC4=CC=CC=C34)=C1)NC5=CC=CC=C5

 

 

Technical Data:

 

Appearance: white 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

 

In Vitro:

A 83-01 is a potent inhibitor of TGF-β type I receptor ALK5 kinase, ALK4 and ALK7, reduces the level of ALK-5-induced transcription with an IC50 of 12 nM in Mv1Lu cells, also blocks the ALK4-TD and ALK7-TD induced transcription with IC50s of 45 nM and 7.5 nM in R4-2 cells, and weakly suppresses that induced by constitutively active ALK-6, ALK-2, ALK-3, and ALK-1. A 83-01 (0.03-10 µM) potently prevents the growth-inhibitory effects of TGF-β, and completely inhibits the effect at 3 µM. A 83-01 (1-10 µM) inhibits TGF-β-induced Smad activation in HaCaT cells[1]. A 83-01 (1 µM) decreases cell motility, adhesion and invasion increased by TGF-β1 in HM-1 cells, but does not change cell proliferation.

 

In Vivo

A 83-01 (50, 150 and 500 μg/mouse, i.p.) significantly improves survival of the mice without body weight or neurobehavioral appearances. A 83-01 (0.5 mg/kg, i.p.) shows a significantly strong antitumor effect in mice bearing M109 cells.

 

 

References

 

  1. Spinato S, Galindo-Moreno P, Zaffe D, Bernardello F, Soardi CM. Is socket healing conditioned by buccal plate thickness? A clinical and histologic study 4 months after mineralized human bone allografting. Clin Oral Implants Res. 2012 Nov 21. doi: 10.1111/clr.12073. [Epub ahead of print] PubMed PMID: 23167308.

 

  1. Chen WP, Wu SM. Small molecule regulators of postnatal Nkx2.5 cardiomyoblast proliferation and differentiation. J Cell Mol Med. 2012 May;16(5):961-5. doi: 10.1111/j.1582-4934.2011.01513.x. PubMed PMID: 22212626; PubMed Central PMCID: PMC3325363.

 

  1. Shimada H, Hashimoto Y, Nakada A, Shigeno K, Nakamura T. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia. Biochem Biophys Res Commun. 2012 Jan 13;417(2):659-64. doi: 10.1016/j.bbrc.2011.11.111. Epub 2011 Dec 8. PubMed PMID: 22172948.

 

  1. Vogt J, Traynor R, Sapkota GP. The specificities of small molecule inhibitors of the TGFß and BMP pathways. Cell Signal. 2011 Nov;23(11):1831-42. doi: 10.1016/j.cellsig.2011.06.019. Epub 2011 Jun 29. PubMed PMID: 21740966.

 

  1. Yamamura S, Matsumura N, Mandai M, Huang Z, Oura T, Baba T, Hamanishi J, Yamaguchi K, Kang HS, Okamoto T, Abiko K, Mori S, Murphy SK, Konishi I. The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer. Int J Cancer. 2012 Jan 1;130(1):20-8. doi: 10.1002/ijc.25961. Epub 2011 Apr 18. PubMed PMID: 21503873.

 

Products are for research use only. Not for human use.

 

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