Home DNA Damage/DNA Repair PARP inhibitor BMN-673 (Talazoparib)

연구용

BMN-673 (Talazoparib) PARP inhibitor

제품 번호: S7048

Talazoparib (BMN 673, LT-673) is a novel PARP inhibitor with IC50 of 0.57 nM for PARP1 in a cell-free assay. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 3.
BMN-673 (Talazoparib) PARP inhibitor Chemical Structure

화학 구조

분자량: 380.35

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품질 관리 (Quality Control)

배치: 순도: 99.88%
99.88

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
BR5FVB1-Akt Growth Inhibition Assay 0.1-100 nM 24/48/72 h inhibits cell proliferation dose dependently 26047697
BR5FVB1-Akt Apoptosis Assay 0.1-100 nM 72 h induces apoptosis 26047697
Capan-1 Growth Inhibition Assay IC50=16.0 ± 5.4 µM  25864590
MIA PaCa-2 Growth Inhibition Assay IC50=58.23 ± 8.1 µM  25864590
RD Growth Inhibition Assay IC50=8.7 nM 25263539
Rh41 Growth Inhibition Assay IC50=8.1 nM 25263539
Rh18 Growth Inhibition Assay IC50=4.9 nM 25263539
Rh30 Growth Inhibition Assay IC50=31.1 nM 25263539
BT-12 Growth Inhibition Assay IC50> 1,000 nM 25263539
CHLA-266 Growth Inhibition Assay IC50> 1,000 nM 25263539
TC-71 Growth Inhibition Assay IC50=3.7 nM 25263539
CHLA-9 Growth Inhibition Assay IC50=8.2 nM 25263539
CHLA-10 Growth Inhibition Assay IC50=67.8 nM 25263539
CHLA-258 Growth Inhibition Assay IC50=4.6 nM 25263539
SJ-GBM2 Growth Inhibition Assay IC50=16.2 nM 25263539
NB-1643 Growth Inhibition Assay IC50=18.4 nM 25263539
NB-EBc1 Growth Inhibition Assay IC50=25.8 nM 25263539
CHLA-90 Growth Inhibition Assay IC50> 1,000 nM 25263539
CHLA-136 Growth Inhibition Assay IC50=14.2 nM 25263539
NALM-6 Growth Inhibition Assay IC50=49 nM 25263539
COG-LL-317 Growth Inhibition Assay IC50=9.4 nM 25263539
RS4;11 Growth Inhibition Assay IC50=52.6 nM 25263539
MOLT-4 Growth Inhibition Assay IC50=16.6 nM 25263539
CCRF-CEM Growth Inhibition Assay IC50=697.3 nM 25263539
Kasumi-1 Growth Inhibition Assay IC50=786.2 nM 25263539
Karpas-299 Growth Inhibition Assay IC50=75.7 nM 25263539
Ramos-RA1 Growth Inhibition Assay IC50=68.3 nM 25263539
DT40 Growth Inhibition Assay IC50=4 nM 24356813
DU145 Growth Inhibition Assay IC50=11 nM 24356813
H209 Growth Inhibition Assay IC50=1.7 nM 24077350
H1048 Growth Inhibition Assay IC50=2.2 nM 24077350
H524 Growth Inhibition Assay IC50=3.1 nM 24077350
H1930 Growth Inhibition Assay IC50=4.1 nM 24077350
H69 Growth Inhibition Assay IC50=5.2 nM 24077350
H2081 Growth Inhibition Assay IC50=6.3 nM 24077350
H2107 Growth Inhibition Assay IC50=7.3 nM 24077350
H1092 Growth Inhibition Assay IC50=8.9 nM 24077350
DMS-79 Growth Inhibition Assay IC50=9.3 nM 24077350
H446 Growth Inhibition Assay IC50=13 nM 24077350
COR-L279 Growth Inhibition Assay IC50=15 nM 24077350
LoVo Function assay 30 mins EC50 = 0.0025 μM 25761096
MX1 Cytotoxicity assay EC50 = 0.0003 μM 26652717
LoVo Function assay 30 mins EC50 = 0.00251 μM 26652717
LoVo Cytotoxicity assay 0.4 uM 5 days GI50 = 0.004 μM 26652717
Capan1 Cytotoxicity assay EC50 = 0.005 μM 26652717
MRC5 Cytotoxicity assay EC50 = 0.31 μM 26652717
MX1 Function assay 1 mg/kg 2 ,8 and 24 hrs Decrease in PAR level in athymic nu/nu mouse xenografted with human MX1 cells at 1 mg/kg, po administered as single dose measured after 2 ,8 and 24 hrs by ELISA 26652717
MX1 Antitumor assay 0.33 mg/kg 28 days Antitumor activity against BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse at 0.33 mg/kg, po qd administered for 28 days 26652717
MX1 Antitumor assay 0.165 mg/kg 28 days Antitumor activity against BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse assessed as tumor growth inhibition at 0.165 mg/kg, po administered twice a day for 28 days 26652717
MX1 Function assay 0.33 mg/kg Potentiation of carboplatin-induced tumor growth inhibition of BRCA1 deficient human MX1 cells xenografted in athymic nu/nu mouse at 0.33 mg/kg po and animals were treated with carboplatin at 35 mg/kg, ip on day 1 26652717
MDA-MB-436 Antiproliferative assay 7 days IC50 = 0.0007 μM 28692916
Capan1 Antiproliferative assay 7 days IC50 = 0.0018 μM 28692916
VC8 Cytotoxicity assay 3 days IC50 = 0.0042 μM 28692916
V79 Cytotoxicity assay 3 days IC50 = 5.0114 μM 28692916
Capan1 Function assay 0.1 uM 4 hrs Inhibition of PARP1 in BRCA2 deficient human Capan1 cells assessed as increase in PARP1-DNA trapping at 0.1 uM after 4 hrs by Western blot analysis 28692916
MDA-MB-436 Function assay 1 uM 4 hrs Inhibition of PARP1 in BRCA1 deficient human MDA-MB-436 cells assessed as increase in PARP1-DNA trapping at 1 uM after 4 hrs by Western blot analysis 28692916
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 380.35 화학식

 

C19H14F2N6O
 
 보관 (수령일로부터)
CAS 번호 1207456-01-6 -- 원액 보관

동의어 LT-673 Smiles CN1C(=NC=N1)C2C(NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F

용해도 (Solubility)

In vitro
배치:

DMSO : 19 mg/mL (49.95 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)

특징
Most potent and selective PARPi reported thus far.
Targets/IC50/Ki
PARP1
(Cell-free assay)
0.57 nM
시험관 내(In vitro)

BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. BMN 673 selectively kills cancer cells with BRCA-1 or BRCA-2 mutations. BMN 673 demonstrates single-agent cytotoxicityin BRCA-1 mutant (MX-1, IC50 = 0.3 nM) and BRCA-2 mutant cells (Capan-1, IC50 = 5 nM). In contrast, in MRC-5 normal human fibroblastand other tumor cell lines with wild-type BRCA-1 and BRCA-2 genes, IC50 of BMN 673 ranges between 90 nM and 1.9 μM.

Off-target molecular screening did not identify significant non-specific activity for this class of PARP inhibitors.
생체 내(In vivo)

In rat pharmacokinetic studies, BMN 673 displays >50% oralbioavailability and pharmacokinetic properties that enable singledaily dosing. In MX-1 xenograft tumor model studies, daily oral dosingof BMN 673 significantly enhances the antitumor effects ofcytotoxic therapies in a dose-dependent manner.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot pKAP1 / pChk2 / pChk1 cleaved-PARP / cleaved-caspase3 / γ-H2AX p-ATM PD-L1
S7048-WB2
28947502
Growth inhibition assay Cell viability
S7048-viability1
29158830
Immunofluorescence cleaved PARP / 53BP1 RAD51
S7048-IF1
28958991

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT05425862 Suspended
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Peter MacCallum Cancer Centre Australia
 October 21 2022 Phase 1
NCT05141708 Completed
Metastatic Breast Cancer|Breast Neoplasms
Pfizer
 December 17 2021 --
NCT05053854 Recruiting
Neuroendocrine Tumors
Peter MacCallum Cancer Centre Australia
 December 8 2021 Phase 1
NCT04991480 Active not recruiting
Advanced Cancer|Metastatic Cancer|Breast Cancer
Artios Pharma Ltd
 September 13 2021 Phase 1|Phase 2
NCT04987931 Completed
Breast Cancer
Pfizer
 August 20 2021 --

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Which solvent do you recommend to dilute it for in vivo study in mice?

답변:
According to the paper: http://clincancerres.aacrjournals.org/content/19/18/5003.full, it can be dissolved in vehicle (10% DMAc, 6% Solutol, and 84% PBS). Quote from Method and Material section "Xenograft experiments: BMN 673 (various doses as indicated), or vehicle (10% DMAc, 6% Solutol, and 84% PBS) was administered by oral gavage"