167465-36-3 Usage
Chemical Properties
Pale Yellow Solid
Uses
Multi-drug resistance (MDR) modulator; selective inhibitor of P-glycoprotein (P-gp). Antineoplastic adjunct (chemosensitizer).
Biological Activity
ly335979 is a selective inhibitor of p-gp with ic50 value of 1.2 nm [1, 2].p-gp (p-glycoprotein) is a member of atp-binding cassette (abc) transporters and plays a pivotal role in pumping many foreign substances out of cells. it has been reported that abnormal expression of p-gp is correlated with the multidrug resistance of tumor cells [3].ly335979 is a potent p-gp inhibitor and has a different selectivity with the reported p-gp inhibitor cyclosporin a or verapamil. in drug-resistant cell line hl60/vcr with highly expression of p-gp, ly335979 exhibited highly restore ability of p-gp than cyclosporin a or verapamil and the ic 50 value of 1.2 nm [1]. when tested with a panel of cell lines over-expressed p-gp (cem/vlb100, mcf-7/adr, 2780ad, p388/adr, and ucla-p3.003vlb), administration of ly335979 reversed the cells resistance to vinblastine, doxorubicin, btoposide and taxol by inhibiting p-gp activity [2].in female nude mice model with ucla-p3.003vlb mdr tumor cells subcutaneous xenograft, pre-treated with ly335979 (30mg/kg) restored tumor cells sensitivity to taxol (20 mg/kg) which combination markedly suppressed solid tumor growth compared with control group [2].
references
1. green, l.j., p. marder, and c.a. slapak, modulation by ly335979 of p-glycoprotein function in multidrug-resistant cell lines and human natural killer cells. biochem pharmacol, 2001. 61(11): p. 1393-9.2. dantzig, a.h., et al., reversal of p-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, ly335979. cancer res, 1996. 56(18): p. 4171-9.3. hu, t., et al., reversal of p-glycoprotein (p-gp) mediated multidrug resistance in colon cancer cells by cryptotanshinone and dihydrotanshinone of salvia miltiorrhiza. phytomedicine, 2014. 21(11): p. 1264-72.
Check Digit Verification of cas no
The CAS Registry Mumber 167465-36-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,7,4,6 and 5 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 167465-36:
(8*1)+(7*6)+(6*7)+(5*4)+(4*6)+(3*5)+(2*3)+(1*6)=163
163 % 10 = 3
So 167465-36-3 is a valid CAS Registry Number.
InChI:InChI=1/C32H31F2N3O2.ClH/c33-32(34)29-22-7-1-3-9-24(22)31(25-10-4-2-8-23(25)30(29)32)37-17-15-36(16-18-37)19-21(38)20-39-28-13-5-12-27-26(28)11-6-14-35-27;/h1-14,21,29-31,38H,15-20H2;1H/t21?,29-,30+,31?;
167465-36-3Relevant articles and documents
Stereochemistry of C-6 nucleophilic displacements on 1,1- difluorocyclopropyldibenzosuberanyl substrates. An improved synthesis of multidrug resistance modulator LY335979 trihydrochloride
Barnett, Charles J.,Huff, Bret,Kobierski, Michael E.,Letourneau, Michael,Wilson, Thomas M.
, p. 7653 - 7660 (2007/10/03)
Studies of the displacement chemistry of 1,1- difluorocyclopropyldibenzosuberanyl alcohol 4 and its activated bromide derivative 6 have led to an improved approach to anti-2, a key precursor to LY335979 3HCl (1). Bromination of either syn-4 or anti-4 gave
