AZD-7762

Cas No.:	860352-01-8
Chemical Name:	(S)-5-(3-Fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide
Synonyms:	AZD 7762;5-(3-Fluorophenyl)-3-ureidothiophene-N-[(S)-piperidin-3-yl]-2-carboxamide;(S)-5-(3-Fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide;3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide;3-[(aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-Thiophenecarboxamide;AZD-7762;AZD7762 (AZD-7762);AZD 7762,AZD7762;AZD7762;5D822Y3L1H;5-(3-Fluorophenyl)-N-[(3s)-3-Piperidyl]-3-Ureido-Thiophene-2-Carboxamide;IAYGCINLNONXHY-LBPRGKRZSA-N;YDJ;AZD7762 hydrochloride;GTPL7713;AOB1915
SMILES:	O=C(C1=C(NC(N)=O)C=C(C2=CC=CC(F)=C2)S1)N[C@@H]3CNCCC3
Formula:	C17H19FN4O2S
M.Wt:	362.4218
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	AZD-7762 is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with an IC50 of 5 nM for Chk1.
In Vivo:	In the rat H460-DNp53 xenograft study, AZD-7762 (AZD7762) potentiates the antitumor activity of Gemcitabine in a dose-dependent manner by a decrease in %T/C with increasing dose (48% and 32%, 10 and 20 mg/kg AZD-7762, respectively). In the mouse xenograft study in combination with Irinotecan, SW620 established tumors are treated with vehicle, Irinotecan alone, AZD-7762 alone, or AZD-7762 in combination with Irinotecan. AZD-7762 dosed alone shows insignificant antitumor activity, whereas Irinotecan alone displays striking and significant activity (%T/C with increasing dose is 9 and 1, respectively ). In combination with AZD-7762, %T/C increases significantly to -66% and -67%, respectively[1]. AZD7762 combination with CX-5461 induces cancer cell death of Tp53-null (Tp53-/-) Eμ-Myc lymphoma cells in vitro and in vivo[2].
In Vitro:	AZD-7762 (AZD7762) is an equally potent inhibitor of Chk1 and Chk2 in vitro. AZD-7762 potently inhibits Chk1 and Chk2, abrogates DNA damage-induced S and G2 checkpoints, enhances the efficacy of gemcitabine and topotecan, and modulates downstream checkpoint pathway proteins. AZD-7762 potently inhibits Chk1 phosphorylation of a cdc25C peptide with an IC50 of 5 nM as measured by a scintillation proximity assay. The Ki for AZD-7762 is determined to be 3.6 nM. Kinetic characterization suggests that AZD-7762 binds in the ATP-binding site of Chk1 and is thought to compete directly for ATP binding in a reversible manner. AZD-7762 is shown to abrogate the G2 arrest induced by Camptothecin with an average EC50 of 10 nM (n=12) and maximal abrogation in the range of 100 nM[1].