Home Ubiquitin E3 ligase Ligand chemical Pomalidomide (CC-4047)

연구용

Pomalidomide (CC-4047) Immunomodulatory agent

제품 번호: S1567

Pomalidomide inhibits LPS-induced TNF-α release with IC50 of 13 nM in PBMCs. Pomalidomide can be utilized in PROTAC as a ligand for targeting E3 ligase and inhibiting the E3 ligase protein cereblon (CRBN). Pomalidomide promotes apoptosis and cell cycle arrest.
Pomalidomide (CC-4047) E3 ligase Ligand chemical Chemical Structure

화학 구조

분자량: 273.24

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품질 관리 (Quality Control)

배치: 순도: 99.98%
99.98

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
MOLP-8 Cytotoxicity Assay 10 μM 24 h potently augments direct and indirect MM cell killing by SAR 26338273
J-CD38 Cytotoxicity Assay 10 μM 24 h potently augments direct and indirect MM cell killing by SAR 26338273
R-CD38 Cytotoxicity Assay 10 μM 24 h potently augments direct and indirect MM cell killing by SAR 26338273
BC-3 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=107 nM, inhibits cell IC50=107 nM, viability dose dependently 26119939
BCBL-1 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=74 nM, inhibits cell viability dose dependently 26119939
JSC-1 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=34 nM, inhibits cell viability dose dependently 26119939
VG-1 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=101 nM, inhibits cell viability dose dependently 26119939
UMPEL-1 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=32 nM, inhibits cell viability dose dependently 26119939
UMPEL-3 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=111 nM, inhibits cell viability dose dependently 26119939
BC-1 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=744 nM, inhibits cell viability dose dependently 26119939
BCP-1 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=396 nM, inhibits cell viability dose dependently 26119939
APK-1 Growth Inhibition Assay 39-1250 nM 5 d DMSO  IC50=226 nM, inhibits cell viability dose dependently 26119939
RPMI8226  Growth Inhibition Assay 0.01-50 μM 48 h DMSO  IC50=8 μM 26097872
OPM2  Growth Inhibition Assay 0.01-50 μM 48 h DMSO  IC50=10 μM 26097872
RPMI8226  Function Assay 10 μM 48 h DMSO  strengthens cytoplasmic-nuclear shuttling of mTOR and p-mTOR protein 26097872
OPM2  Function Assay 10 μM 48 h DMSO  strengthens cytoplasmic-nuclear shuttling of mTOR and p-mTOR protein 26097872
RPMI8226 Function Assay 0.1-10 μM 4 h DMSO  increases VEGF mRNA expression 25053990
SH-SY5Y  Apoptosis Assay 25 μg/mL 1 h causes statistically significant reduction in both CPF- and CPF+CM-induced apoptosis  24975276
JJN3 Growth Inhibition Assay 0.1-100 μM 72 h DMSO inhibits cell growth slightly 23178378
XG-1 Growth Inhibition Assay 0.1-100 μM 72 h DMSO inhibits cell growth 23178378
CD138+  Growth Inhibition Assay 0.1-100 μM 72 h DMSO inhibits cell growth 23178378
XG-1 Function Assay 2/100 μM 24 h DMSO inhibits CCL3/MIP-1α mRNA expression 23178378
U266 Growth Inhibition Assay 0.01-10 μM 48 h DMSO inhibits cell growth dose dependently 22552008
CRBN60 Growth Inhibition Assay 0.01-10 μM 48 h DMSO inhibits cell growth dose dependently 22552008
CRNB75 Growth Inhibition Assay 0.01-10 μM 48 h DMSO inhibits cell growth dose dependently 22552008
MM.1S Growth Inhibition Assay 0.01-10 μM 48 h DMSO significantly inhibits proliferation at concentrations as low as 0.01μM 21389327
OPM2 Growth Inhibition Assay 0.01-10 μM 48 h DMSO significantly inhibits proliferation at concentrations as low as 0.01μM 21389327
MM.1S Function Assay 10 μM 72 h DMSO significantly decreases the protein level of C/EBPβ isoforms  21389327
H929 Function Assay 10 μM 72 h DMSO significantly decreases the protein level of C/EBPβ isoforms  21389327
OPM2 Function Assay 10 μM 72 h DMSO significantly decreases the protein level of C/EBPβ isoforms  21389327
CT26 Function Assay 1/10 μM 24 h reduces the numbers of live colonies  19638977
T-cells Function assay 2 to 3 days Inhibition of IL-2 production in human T cells measured after 2 to 3 days by ELISA, EC50 = 0.008 μM. 23168019
DF15 Function assay 4 hrs Induction of cereblon-mediated aiolos degradation in human DF15 cells expressing ePL-tagged aiolos after 4 hrs by luminometric analysis, EC50 = 0.022 μM. 28425720
DF15 Function assay 4 hrs Induction of cereblon-mediated ikaros degradation in human DF15 cells expressing ePL-tagged ikaros after 4 hrs by luminometric analysis, EC50 = 0.024 μM. 28425720
DF15 Function assay 4 hrs Induction of CRL4/CRBN ubiquitin ligase-mediated aiolos degradation in human DF15 cells expressing pLOC-ePL-tagged aiolos after 4 hrs by luminescence based beta-galactosidase enzyme fragmentation complementation assay, EC50 = 0.027 μM. 28358507
NAMALWA Antiproliferative assay 72 hrs Antiproliferative activity against human NAMALWA cells assessed as inhibition of [3H]thymidine incorporation after 72 hrs by scintillation counting, IC50 = 0.03 μM. 23168019
HeLa Function assay Inhibition of IL-1-alpha-induced NF-kappaB activation in HeLa cells assessed as blocking of p50/p65 nuclear translocation, IC50 = 1.27 μM. 17845850
DF15 Function assay 0.01 to 1 uM 5 hrs Induction of cereblon-mediated aiolos degradation in human DF15 cells at 0.01 to 1 uM after 5 hrs by immunoblot analysis 28425720
OPM2 Function assay 0.01 to 1 uM 5 hrs Induction of cereblon-mediated ikaros degradation in human OPM2 cells at 0.01 to 1 uM after 5 hrs by immunoblot analysis 28425720
DF15 Function assay 0.01 to 1 uM 5 hrs Induction of cereblon-mediated ikaros degradation in human DF15 cells at 0.01 to 1 uM after 5 hrs by immunoblot analysis 28425720
OPM2 Function assay 0.01 to 1 uM 5 hrs Induction of cereblon-mediated aiolos degradation in human OPM2 cells at 0.01 to 1 uM after 5 hrs by immunoblot analysis 28425720
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 273.24 화학식

C13H11N3O4

 보관 (수령일로부터)
CAS 번호 19171-19-8 SDF 다운로드 원액 보관

동의어 CC-4047 Smiles C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)N

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (365.97 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
A derivative of thalidomide and up to 10,000 times more potent than thalidomide.
Targets/IC50/Ki
CRBN
TNF-α
(PBMCs)
13 nM
시험관 내(In vitro)

Pomalidomide inhibits lipopolysaccharide (LPS) stimulated TNF-alpha release in human PBMC and in human whole blood with IC50 values of 13 nM and 25 nM, respectively. This compound inhibits the growth of T regulatory cells which is stimulated by IL-2 with an IC50 of ~1 μM. Treatment with this chemical (6.4 nM-10 μM) increases the production of IL-2 in human peripheral blood T cells, and is slightly more potent in the CD4+ subset than in the CD8+ subset. It is significantly more potent than CC-5013 at elevating IL-2, IL-5, and IL-10 levels, but only slightly more potent than CC-5013 at elevating IFN-γ levels. This agent enhances SEE and Raji cells induced AP-1 transcriptional activity in Jurkat cells in a dose-dependent manner, with a maximal enhancement of 4-fold at 1 μM. Exposure of Raji cells to various concentrations of this compound (2.5-40 μg/mL) for 48 hours leads to a significant decrease in cell proliferation and DNA synthesis. There is a reduction of ~40% compared to vehicle-treated controls.

키나아제 분석
Inhibition of TNF-α synthesis
TNF-α inhibitory activity is measured in lipopolysacharide (LPS) stimulated PBMC. Pomalidomide is added to human PBMCs 1 hour prior to the addition of LPS (1 μg/mL) and incubation continued for an additional 18-20 hours. Supernatants are then harvested, and the concentration of TNF-α in the supernatants is determined by ELISA. The concentration of this compound that inhibits TNF- production by 50% (IC50) is calculated by nonlinear regression analysis. The human whole blood TNF- inhibition assay is run in a similar fashion to the PBMC assay except that heparinized fresh human whole blood is plated directly into microtiter plates.
생체 내(In vivo)

Pomalidomide enhances the antitumor effect of rituximab against B-cell lymphomas in severe combined immunodeficient mice. Administration of this compound in combination with rituximab, gives the mice a median survival period of 74 days compared with 58 days of CC5013/rituximab treatment and 45 days of rituximab nonotherapy. The synergistic effect of this compound and rituximab can be completely abrogated by depletion of NK cells, supporting the proposal that NK cell expansion is one mechanism by which this compound may augment rituximab antitumor activity.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/16115943/
  • [5] https://pubmed.ncbi.nlm.nih.gov/26051217/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot CEBPβ IKZF1 / IKZF3 / UBE2G1 / CRBN
S1567-WB1
21389327
Immunofluorescence IKZF1
S1567-IF1
29496670

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT04902443 Recruiting
Viral Associated Malignancies|Kaposi Sarcoma|EBV/KSHV-associated Lymphomas
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 December 10 2021 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Is the formulation S1567 in 1% DMSO+30% polyethylene glycol+1% Tween 80 suitable for its oral administration?

답변:
Its suspension in 1% DMSO+30% polyethylene glycol+1% Tween 80 is for oral gavage.

질문 2:
I would like to know if it is racemic or optically active?

답변:
Our S1567 is racemic.