GDC-0084
- Product Name
- GDC-0084
- CAS No.
- 1382979-44-3
- Chemical Name
- GDC-0084
- Synonyms
- RG7666;CS-2290;RG-7666;GDC-0084;RG 7666);Paxalisib;GDC-0084(RG7666);GDC-0084 (GDC0084;GDC-0084 (Paxalisib;Paxalisib (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
- form
- Solid
- pka
- 2.62±0.40(Predicted)
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
N-Bromosuccinimide Price
- Product number
- FD145121
- Product name
- GDC 0084
- Packaging
- 1mg
- Price
- $60
- Updated
- 2021/12/16
- Product number
- FD145121
- Product name
- GDC 0084
- Packaging
- 2mg
- Price
- $94
- Updated
- 2021/12/16
- Product number
- B7826
- Product name
- GDC-0084
- Packaging
- 1mg
- Price
- $95
- Updated
- 2021/12/16
- Product number
- 4658DN
- Product name
- Gdc-0084
- Packaging
- 1mg
- Price
- $131
- Updated
- 2021/12/16
- Product number
- B7826
- Product name
- GDC-0084
- Packaging
- 10mM(in 1mL DMSO)
- Price
- $158
- Updated
- 2021/12/16
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).
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.
GDC-0084 Preparation Products And Raw materials
Raw materials
Preparation Products
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View Lastest Price from GDC-0084 manufacturers
- Product
- 5-[6,6-Dimethyl-4-(4-morpholinyl)-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl]-2-pyrimidinamine 1382979-44-3
- Price
- US $1.00/KG
- Min. Order
- 1KG
- Purity
- Min98% HPLC
- Supply Ability
- g/kg/ton
- Release date
- 2019-12-20