GDC-0980

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GDC-0980 (Apitolisib, GNE 390, RG 7422) 是一种有效的、选择性的、口服的 I 类 PI3K/mTOR 抑制剂，对 PI3Kα/β/δ/γ 的 IC50 为 5 nM/27 nM/7 nM/14 nM，抑制mTOR 抑制剂，Ki 为 17 nM。

GDC-0980 (Apitolisib, GNE 390, RG 7422) is a potent, selective, orally available class I PI3K/mTOR inhibitor with IC50 of 5 nM/27 nM/7 nM/14 nM for PI3Kα/β/δ/γ, inhibits mTOR inhibitor with Ki of 17 nM; displays remarkably selective for several other members of the closely related PIKK family kinases, including C2alpha, C2beta, VPS34 I, PI4Kalpha, PI4Kbeta and DNA-PK; potently inhibits signal transduction downstream of both PI3K and mTOR, reduces viability in multiple cancer cell lines by cell-cycle inhibition and induction of apoptosis (prostate IC50<200 nM, NSCLC lines <200 nM); potently inhibits tumor growth in xenograft models with activated PI3K, loss of LKB1 or PTEN.Breast Cancer Phase 2 Clinical(In Vitro):Apitolisib (GDC-0980) is remarkably selective for several other members of the closely related PIKK family kinases: C2alpha IC50=1300 nM; C2beta IC50=7 94 nM; VPS34 IC50=2000 nM; PI4Kalpha >10 μM; PI4Kbeta >10 μM; DNA-PK Kiapp=623 nM, respectively. A recent study shows that Apitolisib (GDC-0980) reduces cancer cell viability by inhibiting cell-cycle procession and inducing apoptosis with most potency in prostate (IC50 < 200 nM 50%), <500 nM 100%), breast (IC50 <200 nM 37%, <500 nM 78%) and NSCLC lines (IC50 <200 nM 29%, <500 nM 88%) and less potency in pancreatic (IC50 <200 nM 13%, <500 nM 67%) and melanoma cell lines (IC50 <200 nM 0%, <500 nM 33%).(In Vivo):Apitolisib (GDC-0980) (1 mg/kg, p.o.) demonstrats significant efficacy in mouse xenografts and is currently in phase I clinical trials for cancer. Clearance and PPB are low, and Apitolisib (GDC-0980) shows dose-proportional exposure from 5 mg/kg dosed in PEG to 50 mg/kg dosed in suspension in MCT, a finding attributed partially to the compound’s good solubility. Apitolisib (GDC-0980) (5 mg/kg, p.o.) results in greater than 50% TGI in 15 of the 20 xenograft models. The difference in tumor response to Apitolisib (GDC-0980) treatment correlates with the duration of knockdown of pAkt/tAkt.

Apitolisib (GDC-0980) is remarkably selective for several other members of the closely related PIKK family kinases: C2alpha IC50=1300 nM; C2beta IC50=7 94 nM; VPS34 IC50=2000 nM; PI4Kalpha >10 μM; PI4Kbeta >10 μM; DNA-PK Kiapp=623 nM, respectively. A recent study shows that Apitolisib (GDC-0980) reduces cancer cell viability by inhibiting cell-cycle procession and inducing apoptosis with most potency in prostate (IC50 < 200 nM 50%), <500 nM 100%), breast (IC50 <200 nM 37%, <500 nM 78%) and NSCLC lines (IC50 <200 nM 29%, <500 nM 88%) and less potency in pancreatic (IC50 <200 nM 13%, <500 nM 67%) and melanoma cell lines (IC50 <200 nM 0%, <500 nM 33%).

Apitolisib (GDC-0980) (1 mg/kg, p.o.) demonstrats significant efficacy in mouse xenografts and is currently in phase I clinical trials for cancer. Clearance and PPB are low, and Apitolisib (GDC-0980) shows dose-proportional exposure from 5 mg/kg dosed in PEG to 50 mg/kg dosed in suspension in MCT, a finding attributed partially to the compound’s good solubility. Apitolisib (GDC-0980) (5 mg/kg, p.o.) results in greater than 50% TGI in 15 of the 20 xenograft models. The difference in tumor response to Apitolisib (GDC-0980) treatment correlates with the duration of knockdown of pAkt/tAkt.

Apitolisib | GNE 390 | GDC0980 | RG 7422

PI3K/Akt/mTOR signaling

PI3K

mTOR|p110α|p110β|p110γ|p110δ

Cancer

Breast Cancer

1032754-93-0

498.6011

C23H30N8O3S

>98% (HPLC)

10 mM in DMSO

C[C@H](O)C(N1CCN(CC2=C(C)C3=NC(C4=CN=C(N)N=C4)=NC(N5CCOCC5)=C3S2)CC1)=O

1-Propanone, 1-[4-[[2-(2-amino-5-pyrimidinyl)-7-methyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]methyl]-1-piperazinyl]-2-hydroxy-, (2S)-

(-20℃)

With Ice Pack

≥ 2 years