Home MAPK Raf inhibitor LY3009120

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LY3009120 Raf inhibitor

제품 번호: S7842

LY3009120 (DP-4978) is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively. This compound induces autophagy. Phase 1.
LY3009120 Raf inhibitor Chemical Structure

화학 구조

분자량: 424.51

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품질 관리 (Quality Control)

배치: 순도: 99.08%
99.08

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
A375 Antiproliferative assay 72 hrs Antiproliferative activity against human A375 cells after 72 hrs by resazurin assay, IC50=0.0092μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.02μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to BRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.031μM. 25965804
A375 Function assay 72 hrs Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ERK phosphorylation measured after 72 hrs by ELISA assay, IC50=0.037μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to ZAK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.039μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to CRAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.042μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to ARAF in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.044μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to p38 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.061μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to FYN in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.091μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to MAP3K1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.098μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to EphB4 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.1μM. 25965804
HCT116 Function assay Inhibition of KRAS G13D mutant in human HCT116 cells assessed as inhibition of ERK phosphorylation by ELISA, IC50=0.15μM. 25965804
A375 Function assay In vivo inhibition of BRAF V600E mutant in human A375 cells xenografted in po dosed NIH nude rat assessed as plasma concentration required to inhibit ERK phosphorylation by 50%, INH=0.165μM. 25965804
HCT116 Antiproliferative assay 67 hrs Antiproliferative activity against human HCT116 cells after 67 hrs by resazurin assay, IC50=0.22μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to CSK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.29μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to SRC in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.31μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to ABL in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.38μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to IRAK1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.39μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to GCN2 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.45μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to JNK in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.47μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to MAP2K5 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.8μM. 25965804
A375 Function assay 15 mins Competitive binding affinity to KHS1 in human A375 cells after 15 mins in presence of ATP analogue, IC50=0.97μM. 25965804
HCT116 Function assay <100 nM Paradoxical activation of RAS/RAF/MEK signaling pathway in human HCT116 cells expressing wild type BRAF assessed as ERK phosphorylation at <100 nM 25965804
A375 Function assay Inhibition of desthiobiotin-ATP acylphosphate probe binding to B-Raf in human A375 cells by MS analysis, IC50=0.031μM. 30529543
A375 Function assay Inhibition of desthiobiotin-ATP acylphosphate probe binding to C-Raf in human A375 cells by MS analysis, IC50=0.042μM. 30529543
A375 Function assay Inhibition of desthiobiotin-ATP acylphosphate probe binding to A-Raf in human A375 cells by MS analysis, IC50=0.044μM. 30529543
MV4-11 Antiproliferative assay 72 hrs Antiproliferative activity against human MV4-11 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.1μM. 30529543
SK-MEL-2 Antiproliferative assay 72 hrs Antiproliferative activity against human SK-MEL-2 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.2μM. 30529543
A375 Antiproliferative assay 72 hrs Antiproliferative activity against human A375 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.3μM. 30529543
SW579 Antiproliferative assay 72 hrs Antiproliferative activity against human SW579 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM. 30529543
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by Cell-Titer Glo assay, IC50=0.9μM. 30529543
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by Cell-Titer Glo assay, IC50=2.6μM. 30529543
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 424.51 화학식

C23H29FN6O

 보관 (수령일로부터)
CAS 번호 1454682-72-4 SDF 다운로드 원액 보관

동의어 DP-4978 Smiles CC1=CC(=C(C=C1C2=C(N=C3C(=C2)C=NC(=N3)NC)C)NC(=O)NCCC(C)(C)C)F

용해도 (Solubility)

In vitro
배치:

DMSO : 20 mg/mL (47.11 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
C-Raf
(Cell-free assay)
4.3 nM
BRAF(V600E)
(Cell-free assay)
5.8 nM
BRAF WT
(Cell-free assay)
15 nM
시험관 내(In vitro)
LY3009120 inhibits the cell growth of A375 and HCT116 cells with the IC50 of 9.2 and 220 μM, respectively. This compound inhibits the tyrosine kinase KDR with the IC50 of 3.9 μM.
키나아제 분석
Kinase activity measurement using KiNativ assays
Compounds are screened in A375 cell lysates using the ATP-based probe at 5 µM. IC50 values are reported in micromolar units. Cell pellets are resuspended in four volumes of lysis buffer [25 mM Tris pH 7.6, 150 mM NaCl, 1% CHAPS, 1% Tergitol NP-40 type, 1% v/v phosphatase inhibitor cocktail II], sonicated using a tip sonicator, and dounce homogenized. Lysates are cleared by centrifugation at 100,000 g for 30 min. The cleared lysates are filtered through a 0.22 μM syringe filter, and gel filtered into reaction buffer [20 mM Hepes pH 7.8, 150 mM NaCl, 0.1% triton X-100, 1% v/v phosphatase inhibitor cocktail II]. MnCl2 is then added to the lysate to a final concentration of 20 mM prior to inhibitor treatment and probe labeling. Final inhibitor concentrations used for IC50 determinations are 10, 1, 0.1, and 0.01 μM. ATP competition experiments are performed at 1,000, 100, 10, and 1 μM ATP. All inhibitor treatments are performed at room temperature.
생체 내(In vivo)
In rats bearing BRAF V600E ST019VR PDX tumors, LY3009120 (15 or 30 mg/kg, p.o.) shows a dose-dependent tumor growth inhibition. In nude rats bearing A375 xenograft, single dose oral treatment with this compound (3 to 50 mg/kg, p.o.) shows a dose dependent inhibition of phospho-ERK, with a dose for 50% inhibition of phospho-ERK (EC50) of 4.36 mg/kg, with plasma concentration to achieve 50% inhibition of phospho-ERK (EC50) of 68.9 ng/mL or 165 nM.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Beclin-1 / Mcl-1 / LC3 / p62 p-EGFR / EGFR / p-BRAF / BRAF / p-CRAF / CRAF / p-MEK / MEK / p-AKT / AKT
S7842-WB2
28382170

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT02014116 Terminated
Neoplasms|Neoplasm Metastasis|Melanoma|Carcinoma Non-Small-Cell Lung|Colorectal Neoplasms
Eli Lilly and Company
 November 26 2013 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
I am trying to figure out solubility of this compound for in vivo studies. I need some details on the formulation and how it is made to dissolve the chemical?

답변:
It can dissolve in 4% DMSO/30% PEG 300/5% Tween 80/ddH2O at 1 mg/ml clearly, and in 0.5% CMC Na at 30 mg/ml as a suspension.