1429617-90-2 Usage
Uses
Used in Cancer Research and Treatment:
DDR1 Inhibitor 7rh is used as a research chemical compound for studying the role of DDR1 in cancer cell proliferation, invasion, and adhesion. Its application in cancer research aids in understanding the underlying mechanisms of tumorigenesis and the potential for targeted therapies against various types of cancer.
Used in Pharmaceutical Development:
DDR1 Inhibitor 7rh is used as a lead compound in the development of novel pharmaceuticals targeting DDR1. Its potent inhibition of DDR1 makes it a valuable starting point for designing new drugs that can effectively combat cancer by disrupting the signaling pathways involved in cancer cell growth and metastasis.
Used in Drug Delivery Systems:
DDR1 Inhibitor 7rh can be employed as an active ingredient in drug delivery systems, where it can be encapsulated within various carriers, such as organic or metallic nanoparticles, to improve its delivery, bioavailability, and therapeutic outcomes in cancer treatment.
Biochem/physiol Actions
DDR1 Inhibitor 7rh is an orally available, potent, ATP-competitive DDR1-selective inhibitor with in vitro and in vivo anti-cancer efficacy. Compound 7rh is a potent, high affinity (Kd =0.6 nM), ATP-competitive inhibitor against discoidin domain-containing receptor 1 (DDR1; IC50 = 6.8 nM, [ATP] = 100 nM) with significantly reduced potency toward 455 other kinases, including DDR2, Bcr-abl, and c-Kit (IC50 = 101.4 nM, 355 nM and >10 μM, respectively). Inhibitor 7rh reduces DDR1 expression/phosphorylation and downstream signaling in a dose-dependent manner (0.1-2 μM; NCI-H23 NSCLCs), effectively suppressing human cancer cells proliferation (IC50 from 38 nM/K562 to 2.98 μM/NCI-H460) and colony formation (IC50 = 0.56 μM/NCI-H23). Inhibitor 7rh is orally availabe in rats and mice (T1/2 = 15.53 h; Tmax = 4.25 h; Cmax = 1867.5 μg/L, F = 67.4%; 25 mg/kg; rats) and displays in vivo efficacy against Kras (LSLG12Vgeo) tumor growth in mice (50 mg/kg/day p.o.).
Check Digit Verification of cas no
The CAS Registry Mumber 1429617-90-2 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,2,9,6,1 and 7 respectively; the second part has 2 digits, 9 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1429617-90:
(9*1)+(8*4)+(7*2)+(6*9)+(5*6)+(4*1)+(3*7)+(2*9)+(1*0)=182
182 % 10 = 2
So 1429617-90-2 is a valid CAS Registry Number.
1429617-90-2Relevant articles and documents
Discovery and optimization of 3-(2-(Pyrazolo[1,5- a ]pyrimidin-6-yl) ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors
Gao, Mingshan,Duan, Lei,Luo, Jinfeng,Zhang, Lianwen,Lu, Xiaoyun,Zhang, Yan,Zhang, Zhang,Tu, Zhengchao,Xu, Yong,Ren, Xiaomei,Ding, Ke
, p. 3281 - 3295 (2013/06/04)
Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a Kd value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.
