728033-96-3 Usage
Description
OSI-930 is a small molecule inhibitor that targets receptor tyrosine kinases, specifically c-Kit and VEGFR-2. It is known for its ability to inhibit the activity of these kinases, which play a crucial role in various cellular processes, including cell growth, differentiation, and angiogenesis.
Uses
Used in Pharmaceutical Industry:
OSI-930 is used as an inhibitor for receptor tyrosine kinases c-Kit and VEGFR-2 for its ability to block the activity of these proteins, which are involved in cell growth, differentiation, and angiogenesis. This makes OSI-930 a potential therapeutic agent for the treatment of various diseases, including cancer.
Used in Cancer Research:
OSI-930 is used as a research tool to study the role of c-Kit and VEGFR-2 in cancer cell growth and proliferation. By inhibiting these kinases, researchers can gain insights into the molecular mechanisms underlying cancer development and identify potential therapeutic targets for cancer treatment.
Used in Angiogenesis Inhibition:
OSI-930 is used as an inhibitor of VEGFR-2, which plays a critical role in angiogenesis, the process of new blood vessel formation. By targeting VEGFR-2, OSI-930 can potentially inhibit angiogenesis, thereby disrupting the supply of nutrients and oxygen to tumors and limiting their growth.
Used in Drug Development:
OSI-930 is used as a lead compound in the development of new drugs targeting receptor tyrosine kinases. Its potent inhibition of c-Kit and VEGFR-2 makes it a valuable starting point for the design and synthesis of novel therapeutic agents with improved efficacy and selectivity.
Biological Activity
osi-930 is a novel, potent inhibitor of flt1, kinase insert domain receptor (kdr), csf-1r, lck, c-raf and activated receptor tyrosine kinases kit with ic50 values of 8, 9, 15, 22, 41 and 80 nm, respectively [1].osi-930 has been demonstrated to inhibit proliferation and induce apoptosis in the hmc-1 cell line which is highly dependent on kit signaling for survival. on the contrary, osi-930 revealed no growth inhibition of colo-205 cell line under normal culture conditions [1].osi-930 has shown to time- and concentration-dependently inactivate p450 3a4. additionally, osi-930 could reduce co difference spectra of p450 3a4 [2].
references
[1] garton aj1, crew ap, franklin m, cooke ar, wynne gm, castaldo l, kahler j, winski sl, franks a, brown en, bittner ma, keily jf, briner p, hidden c, srebernak mc, pirrit c, o'connor m, chan a, vulevic b,henninger d, hart k, sennello r, li ah, zhang t, richardson f, emerson dl, castelhano al, arnold ld,gibson nw. osi-930: a novel selective inhibitor of kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. cancer res. 2006 jan 15;66(2):1015-24.[2] lin hl1, zhang h, medower c, hollenberg pf, johnson ww. inactivation of cytochrome p450 (p450) 3a4 but not p450 3a5 by osi-930, a thiophene-containing anticancer drug. drug metab dispos. 2011 feb;39(2):345-50.
Check Digit Verification of cas no
The CAS Registry Mumber 728033-96-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,2,8,0,3 and 3 respectively; the second part has 2 digits, 9 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 728033-96:
(8*7)+(7*2)+(6*8)+(5*0)+(4*3)+(3*3)+(2*9)+(1*6)=163
163 % 10 = 3
So 728033-96-3 is a valid CAS Registry Number.
728033-96-3Relevant articles and documents
3-(Benzo[d][1,3]dioxol-5-ylamino)-N-(4-fluorophenyl)thiophene-2-carboxamide overcomes cancer chemoresistance via inhibition of angiogenesis and P-glycoprotein efflux pump activity
Mudududdla, Ramesh,Guru, Santosh K.,Wani, Abubakar,Sharma, Sadhana,Joshi, Prashant,Vishwakarma, Ram A.,Kumar, Ajay,Bhushan, Shashi,Bharate, Sandip B.
, p. 4296 - 4309 (2015/04/14)
3-((Quinolin-4-yl)methylamino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide (OSI-930, 1) is a potent inhibitor of c-kit and VEGFR2, currently under phase I clinical trials in patients with advanced solid tumors. In order to understand the structure-activity relationship, a series of 3-arylamino N-aryl thiophene 2-carboxamides were synthesized by modifications at both quinoline and amide domains of the OSI-930 scaffold. All the synthesized compounds were screened for in vitro cytotoxicity in a panel of cancer cell lines and for VEGFR1 and VEGFR2 inhibition. Thiophene 2-carboxamides substituted with benzo[d][1,3]dioxol-5-yl and 2,3-dihydrobenzo[b][1,4]dioxin-6-yl groups 1l and 1m displayed inhibition of VEGFR1 with IC50 values of 2.5 and 1.9 μM, respectively. Compounds 1l and 1m also inhibited the VEGF-induced HUVEC cell migration, indicating its anti-angiogenic activity. OSI-930 along with compounds 1l and 1m showed inhibition of P-gp efflux pumps (MDR1, ABCB1) with EC50 values in the range of 35-74 μM. The combination of these compounds with doxorubicin led to significant enhancement of the anticancer activity of doxorubicin in human colorectal carcinoma LS180 cells, which was evident from the improved IC50 of doxorubicin, the increased activity of caspase-3 and the significant reduction in colony formation ability of LS180 cells after treatment with doxorubicin. Compound 1l showed a 13.8-fold improvement in the IC50 of doxorubicin in LS180 cells. The ability of these compounds to display dual inhibition of VEGFR and P-gp efflux pumps demonstrates the promise of this scaffold for its development as multi-drug resistance-reversal agents. This journal is
(2-carboxamido)(3-amino)thiophene compounds
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Page/Page column 12, (2008/06/13)
Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-oxide thereof, wherein R1 is R2 is and R3 is C0-4alkyl, are useful in the treatment of cancer.
