ChemicalBook > CAS DataBase List > GDC-0084

GDC-0084

GDC-0084 Structure
GDC-0084
  • CAS No.1382979-44-3
  • Chemical Name:GDC-0084
  • CBNumber:CB93123145
  • Molecular Formula:C18H22N8O2
  • Formula Weight:382.42
  • MOL File:1382979-44-3.mol
GDC-0084 Property
  • Density 1.60±0.1 g/cm3(Predicted)
  • storage temp. Store at -20°C
  • solubility insoluble in H2O; insoluble in EtOH; ≥2.83 mg/mL in DMSO with ultrasonic
  • pka 2.62±0.40(Predicted)
  • form Solid
  • color White to off-white
  • FDA UNII P5DKZ70636
  • NCI Drug Dictionary paxalisib
Hazard and Precautionary Statements (GHS)
  • Symbol(GHS)
  • Signal wordWarning
  • Hazard statements H302-H315-H319-H335
  • Precautionary statements P261-P305+P351+P338

GDC-0084 Chemical Properties,Usage,Production

  • Uses GDC-0084 is an inhibitor of phosphoinositide 3-kinase (PI3K) and mTOR (1,2). Inhibitors of PI3K are useful compounds for developing treatments for brain tumors.
  • Preparation Stumpf et al. at Genentech Inc. (Roche group) developed an efficient multikilogram process to synthesize the brain penetrant PI3K inhibitor, GDC?\0084, a potential drug candidate for the treatment of several brain cancers. An efficient Suzuki coupling reaction between a chloropyrimidine and an arylboronic ester using a palladium catalyst at low loading was reported. The optimized conditions were demonstrated on 6.75 kg of a chloropyrimidine intermediate, providing 7.49 kg of crude GDC?\0084 (94% yield, 99.4% HPLC purity). Using the commercially available XPhos Pd G2 catalyst, instead of the usual PdCl2(dppf)·CH2Cl2 catalyst, it was possible to reduce the catalyst loading from 2 to 0.5 mol%. A final scavenging/recrystallization combination from Si?\Thiol (a solid?\supported resin) and acetic acid/water provided the crude GDC?\0084 with the required purity and polymorphic form (off?\white solid, 6.41 kg, 83% yield, 99.7% HPLC purity).
    1382979-44-3 synthesis
    Genentech’s route to GDC?\0084 employing a pivotal Suzuki reaction.
  • Biological Activity gdc-0084 is a potent and brain penetrant inhibitor of pi3k and mtor with ki values of 2 nm and 70 nm for pi3kα and mtor, respectively [1].glioblastoma (gbm) is the most common primary brain tumor in adults and aberrant pi3k signaling is associated with more than 80% of cases. the pi3k pathway represents a potential target for the treatment of this disease and the inhibitors would need to freely cross the blood-brain barrier (bbb) [1][2].gdc-0084 is a potent and brain penetrant inhibitor of pi3k and mtor. in vitro kinase assay, gdc-0084 exhibited ki values of 2 nm, 46 nm, 3 nm, 10 nm and 70 nm for pi3kα, pi3kβ, pi3kδ, pi3kγ and mtor, respectively. in five different gbm cell lines, gdc-0084 had antiproliferative activities with ec50 values ranging from 0.3 to 1.1 μm. gdc-0084 has excellent human metabolic stability in microsomal and hepatocyte incubations [1]. in transfected cell lines over-expressing human or mouse p-gp or bcrp, gdc-0084 was a poor substrate of these efflux transporters. in mice brain, gdc-0084 significantly lowered pakt and ps6 levels [2].in rats after a 15 mg/kg dose of gdc-0084, the total brain-to-plasma ratio was 1.9-3.3. in subcutaneous u87 glioblastoma tumor xenograft mice model, gdc-0084 significantly inhibited tumor growth in a dose-dependent way. gdc-0084 also concentration-dependently inhibited pakt [1].[1]. heffron tp1, ndubaku co1, salphati l1, et al. discovery of clinical development candidate gdc-0084, a brain penetrant inhibitor of pi3k and mtor. acs med chem lett. 2016 feb 16;7(4):351-6.[2]. salphati l, alicke b, heffron tp, et al. brain distribution and efficacy of the brain penetrant pi3k inhibitor gdc-0084 in orthotopic mouse models of human glioblastoma. drug metab dispos. 2016 dec;44(12):1881-1889. epub 2016 sep 16.
  • in vivo

    After a 25 mg/kg dose of Paxalisib (GDC-0084; Compound 16) administered orally, pAKT in normal mouse brain tissue is significantly inhibited at 1 and 6 h postdose. The potent inhibition of pAKT at both time points in this study demonstrates that Paxalisib inhibits its target behind a fully intact BBB. In addition to the pharmacodynamic effect in normal brain tissue, Paxalisib is studied in a subcutaneous U87 tumor xenograft model of glioblastoma in mice. In this study, Paxalisib achieves significant and dose-dependent tumor growth inhibition. Tumor growth inhibition is first observed at a 2.2 mg/kg dose level. Higher doses led to greater tumor growth inhibition, including tumor regressions at the 17.9 mg/kg dose level. Each of these doses is well tolerated for the duration of the study[1].

  • IC 50 PI3Kα: 2 nM (Ki); PI3Kδ: 3 nM (Ki); PI3Kγ: 10 nM (Ki); PI3Kβ: 46 nM (Ki); mTOR: 70 nM (Ki)
GDC-0084 Preparation Products And Raw materials
Raw materials
Preparation Products
GDC-0084 Suppliers
Global(106)Suppliers
  • Supplier：
    BOC Sciences
  • Tel：+1-631-485-4226
  • Email：inquiry@bocsci.com
  • Country：United States
  • ProdList：19552
  • Advantage：58
  • Supplier：
    career henan chemical co
  • Tel：+86-0371-86658258<br/>+8613203830695
  • Email：factory@coreychem.com
  • Country：China
  • ProdList：29808
  • Advantage：58
  • Supplier：
    TargetMol Chemicals Inc.
  • Tel：+1-781-999-5354<br/>+1-00000000000
  • Email：marketing@targetmol.com
  • Country：United States
  • ProdList：32159
  • Advantage：58
  • Supplier：
    Win-Win chemical CO., Limited
  • Tel：+86-0086-577-64498589<br/>+86-15355981851
  • Email：sales@win-winchemical.com
  • Country：China
  • ProdList：14442
  • Advantage：58
  • Supplier：
    InvivoChem
  • Tel：+1-708-310-1919<br/>+1-13798911105
  • Email：sales@invivochem.cn
  • Country：United States
  • ProdList：6391
  • Advantage：58
  • Supplier：
    TargetMol Chemicals Inc.
  • Tel：
  • Email：support@targetmol.com
  • Country：United States
  • ProdList：38630
  • Advantage：58
GDC-0084 Spectrum
1382979-44-3, GDC-0084Related Search:
  • 化学试剂
  • 高纯试剂
  • 抑制剂
  • 生物试剂
  • 合成有机化合物配体
  • 贝尔卡主打
  • 医药原料
  • 细胞生物学试剂
  • 化合物GDC-0084,10 MM DMSO 溶液
  • 化合物GDC-0084
  • SIM0395
  • PI3K和MTOCHEMICALBOOKR抑制剂(GDC-0084)
  • 5-(6,6-二甲基-4-吗啉-8,9-二氢-6H-[1,4]恶嗪并[4,3-E]嘌呤-2-基)嘧啶-2-胺
  • PI3K和MTOR抑制剂(GDC-0084)
  • 5-[8,9-二氢-6,6-二甲基-4-(4-吗啉基)-6H-[1,4]恶嗪并[4,3-E]嘌呤-2-基]-2-嘧啶胺
  • 1382979-44-3
  • GDC0084, 10 mM in DMSO
  • GDC-0084|||RG7666|||GDC 0084
  • Paxalisib, GDC-0084, RG7666
  • GDC-0084 (Paxalisib
  • Paxalisib (GDC-0084)
  • Paxalisib
  • GDC-0084;GDC 0084;RG7666;RG-7666;RG 7666
  • RG7666; RG-7666; RG 7666; GDC-0084; GDC0084; GDC 0084
  • RG-7666
  • RG7666
  • RG 7666)
  • GDC-0084 (GDC0084
  • CS-2290
  • GDC-0084(RG7666)
  • 5-[6,6-Dimethyl-4-(4-morpholinyl)-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl]-2-pyrimidinamine
  • 2-Pyrimidinamine, 5-[8,9-dihydro-6,6-dimethyl-4-(4-morpholinyl)-6H-[1,4]oxazino[4,3-e]purin-2-yl]-
  • 5-(6,6-dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine
  • 5-[8,9-Dihydro-6,6-dimethyl-4-(4-morpholinyl)-6H-[1,4]oxazino[4,3-e]purin-2-yl]-2-pyrimidinamine
  • GDC-0084

Home

My