GDC-0879

카탈로그 번호S1104 배치:S110407

인쇄

기술 자료

화학식

C19H18N4O2
분자량 334.37 CAS 번호 905281-76-7
용해도 (25°C)* 시험관 내(In vitro) DMSO 66 mg/mL (197.38 mM)
Ethanol 7 mg/mL (20.93 mM)
Water Insoluble
생체 내(In Vivo) (개별적으로 순서대로 용매를 제품에 첨가하십시오.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension
0.5% methylcellulose 0.2% Tween 80

Selleck 연구소에서 검증했습니다. 이 제형에 대한 조정이 필요한 경우 맞춤형 테스트를 위해 당사 영업팀에 문의하십시오.

 10.000mg/ml (29.91mM) Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml은 약간 용해되거나 불용해됨을 의미합니다.
* Selleck은 모든 화합물의 용해도를 자체적으로 테스트하며, 실제 용해도는 게시된 값과 약간 다를 수 있습니다. 이는 정상적인 현상이며, 약간의 배치 간 변동으로 인해 발생합니다.
* 실온 배송 (안정성 테스트 결과 이 제품은 냉각 조치 없이 배송될 수 있음을 보여줍니다.)

원액 준비

생물학적 활성

설명 GDC-0879(AR-00341677)은 A375 및 Colo205 세포에서 0.13 nM의 IC50을 갖는 새롭고 강력하며 선택적인 B-Raf 억제제이며, c-Raf에 대해서도 활성을 나타냅니다. 다른 단백질 키나아제에 대한 억제 작용은 알려진 바 없습니다.
표적
B-Raf
(A375, Colo205 cells)
0.13 nM
시험관 내(In vitro) GDC-0879 also inhibits cellular pERK with IC50 of 63 nM. This compound shows comparable potency in A375 melanoma and Colo205 colorectal carcinoma cell lines, both of which are B-RafV600E mutant, with IC50 of 59 nM and 29 nM for pMEK1 inhibition respectively. It potently inhibits B-RafV600E in Malme3M cells with IC50 of 0.75 μM. This chemical also shows EC50 values < 0.5 μM in many tumor cells (A375, 624, SK-MEL-28, Malme3M, C32, 928, 888, G-361, Colo205, Colo206, SW1417, CL34, and Colo201).
생체 내(In Vivo) In GDC-0879 treated mice, both cell line- and patient-derived BRAFV600E tumors exhibit stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared to mutant KRAS-expressing tumors. Although there is involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression is observed for some KRAS-mutant tumors following this compound administration. Whereas this chemical-mediated efficacy is associated strictly with B-RafV600E status, MEK inhibition also attenuates proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of B-RafV600E melanoma cells to this agent could be dramatically altered by pharmacologic and genetic modulation of PI3K pathway activity.

프로토콜 (참조)

동물 연구:[2]
  • 동물 모델

    Female nu/nu mice

  • 용량

    100 mg/kg

  • 투여

    Oral gavage

참조

  • https://pubmed.ncbi.nlm.nih.gov/19147858/
  • https://pubmed.ncbi.nlm.nih.gov/19276360/

고객 제품 검증

<p> </p><p>Melanoma cell viability and in vivo growth by cyclindependent kinase 2/4 inhibition. Western blot analysis for c-Jun, phosphorylated-ERK1/2 (Thr202/Tyr204) (p-ERK1/2), and total ERK1/2 protein levels was done for human melanoma cell lines treated with the BRAFV600E inhibitor GDC-0879 (1 μM), or MEK inhibitors CI-1040 (1 μM), U0126 (1 μM), and PD98059 (10 μM) for 18 hours.</p>

데이터 출처 [ J Natl Cancer Inst , 2012 , 104(21), 1673-9 ]

<p>Melanoma cell viability and in vivo growth by cyclindependent kinase 2/4 inhibition. In vivo growth of LOXIMVI xenografts in athymic nude Foxn1nu mice is shown. Tumors were allowed to grow to a maximum volume of 250mm<sup>3</sup>, and the mice were subsequently treated daily at the indicated dose levels with CDK2/4 inhibitors by intraperitoneal injection in combination with a BRAFV600E- or MEK-inhibitor. CDK2/4 inhibitor (CVT-313/indolocarbazole CDK4-I) treatment sensitizes tumors to GDC-0879 and CI1040.</p>

데이터 출처 [ J Natl Cancer Inst , 2012 , 104(21), 1673-9 ]

<p>RAF inhibitors induce dimer formation between KSR and RAF, and activate KSR by CRAF. (A) GDC0879 but not PLX4720 induces BRAF/CRAF dimers. Cells overexpressing myc-CRAF and BRAF were treated with drug for 1 h and CRAF immunoprecipitates were immunoblotted for BRAF and CRAF (epitope tagged with myc). (B) GDC0879 but not PLX4720 enhances KSR/BRAF complexes. KSR immunoprecipitates were prepared from cells overexpressing FLAG-KSR and BRAF after treatment with the indicated drug for 1 h and immunoblotted using antibodies to BRAF. (C) Both GDC0879 and PLX4720 induce KSR/CRAF complexes.KSR immunoprecipitates were prepared from cells overexpressing FLAG-KSR and myc-CRAF after treatment with the indicated drug for 1 h and immunoblotted for CRAF using myc antibodies. (D and E) Requirement of KSR for drug-induced ERK activation. Lysates fromwild-type and KSR deficient fibroblasts, transfected with RASV12, were treated with the indicated doses of either GDC-0879 (D) or PLX4720 (E) for 1 h. Lysates were immunoblotted for phospho-ERK1 and 2, ERK2, and RASV12. (F) KSR and CRAF cooperate to activate MEK. Cells expressing the indicated constructs were treated with a 50 μM PLX4720 for 2 h before cell lysates were prepared and analyzed for pMEK by immunoblotting. CRAF(TM) refers to the T421M gatekeeper mutant that cannot bind to the drug(4). (G) KSR in vitro kinase reactions. Cells were cotransfected with WT or ATP binding deficient KSR and CRAF and immunoprecipitates prepared after cells were treated with an activating dose of PLX (10 μM) for 1 h. KSR immunoprecipitates were prepared, pretreated with 50 μM PLX4720 to inhibit coprecipitating RAF activity, and then tested for kinase activity using purified MEK. MEK phosphorylation was detected using a pMEK specific antibody.</p>

데이터 출처 [ Proc Natl Acad Sci USA , 2011 , 108, 6067-6072 ]

<p>B-RafV600E mutated melanoma line, A375, was treated with different doses of GDC0879 for 1 h or 24 h. Cell lysates were analyzed by Western blotting to determine the levels of phosphorylated MEK1/2 (pMEK1/2) and phosphorylated ERK1/2 (pERK1/2).</p><div><div> </div></div><p> </p>

, , Dr. Jong-in Park from Medical College of Wisconsin

Selleck's GDC-0879 인용됨 49 출판물

A structure-based modelling approach identifies effective drug combinations for RAS-mutant acute myeloid leukemia [ bioRxiv, May 03, 2025, nan] PubMed: 40654850
Bioluminescence-based assays for quantifying endogenous protein interactions in live cells [ J Biol Chem, 2025, 301(8):110454] PubMed: 40617353
BH4 Oxidation-Derived H2O2 Activates ERK1/2 Signaling via B-Raf in Rat Dorsal Root Ganglion Neurons [ J Neurochem, 2025, 169(11):e70271] PubMed: 41178527
A structure-based modelling approach identifies effective drug combinations for RAS-mutant acute myeloid leukemia [ bioRxiv, 2025, 2025.04.29.651188] PubMed: 40654850
Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer [ Nature, 2024, 629(8013):927-936] PubMed: 38588697
Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase [ Cell Communication and Signaling, 2023 Jun 14, 136] PubMed: 37316874
BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability [ Sci Adv, 2023, 9(35):eade7486] PubMed: 37656784
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215] PubMed: 36358633
AKT1/FOXP3 axis-mediated expression of CerS6 promotes p53 mutant pancreatic tumorigenesis [ Cancer Lett, 2021, S0304-3835(21)00309-8] PubMed: 34343636

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