Bcl-2 Inhibitors | Inhibitors | 여러 강력하고, 높은 선택성을 가지며, 잘 인용된

Bcl-2 (B-cell lymphoma 2) is the founding pro-survival member of the Bcl-2 protein family, exerting its pro-survival function in response to a broad range of apoptotic stimuli through the inhibition of the mitochondrial outer membrane permeabilization (MOMP) process and the release of mitochondrial cytochrome c.

기타 Apoptosis 억제제

Caspase p53 Ferroptosis PD-1/PD-L1 Survivin TNF-alpha MDM2/MDMX KRas IAP ASK

아이소폼 선택적 제품

Bcl-2 Bcl-B Bcl-w Bcl-xL Mcl-1 Bax Bfl-1 Bad Bcl-xL

Cat.No.	제품명	정보	제품 사용 인용
S8048	ABT-199 (Venetoclax)	Venetoclax (ABT-199, GDC-0199)은 무세포 분석에서 K_i가 <0.01 nM인 Bcl-2 선택적 억제제로, Bcl-xL 및 Bcl-w 대비 4800배 이상 더 선택적이며 Mcl-1에는 활성이 없습니다. Venetoclax는 삼중 음성 유방암 MDA-MB-231 세포에서 세포 성장 억제, Apoptosis, 세포 주기 정지 및 Autophagy를 유도하는 것으로 보고되었습니다. 임상 3상.	Nat Genet, 2026, 58(5):1112-1125. Br J Cancer, 2026, 135(1):152-162 Br J Haematol, 2026, 208(3):905-915
S1001	Navitoclax (ABT-263)	세포 무함유 분석에서 Ki가 ≤ 0.5 nM, ≤1 nM 및 ≤1 nM인 Bcl-xL, Bcl-2 및 Bcl-w의 강력한 억제제인 Navitoclax (ABT-263)는 Mcl-1 및 A1에 더 약하게 결합합니다. 임상 2상.	J Adv Res, 2026, S2090-1232(26)00079-2 Br J Cancer, 2026, 135(1):152-162 EMBO Rep, 2026, 27(10):2526-2548
S8383	S63845	S63845는 0.19 nM의 Kd 값을 가진 새로운 선택적 MCL-1 억제제이며, 다른 BCL-2 계열인 Bcl-2 또는 BCL-XL에는 식별 가능한 결합을 보이지 않습니다.	Biomolecules, July 21, 2020, 1081 Oncogene, January 31, 2022, 1691-1700 Cancer Research Communications, August 1, 2025, 1396-1408
S1002	ABT-737	ABT-737은 Bcl-xL, Bcl-2 및 Bcl-w의 BH3 모방 억제제로, 세포 무함유 분석에서 각각 78.7 nM, 30.3 nM 및 197.8 nM의 EC50을 보이며 Mcl-1, Bcl-B 또는 Bfl-1에 대해서는 억제 효과가 관찰되지 않았습니다. ABT-737은 미토콘드리아 경로 Apoptosis와 Mitophagy를 유도합니다. 임상 2상.	Br J Haematol, 2026, 208(3):905-915 Signal Transduct Target Ther, 2025, 10(1):161 J Hepatol, 2025, S0168-8278(24)02830-7
S7747	Ro-3306	Ro-3306은 20 nM의 K_i 값을 가지며 다양한 인간 키나아제 패널에 대해 15배 이상의 선택성을 보이는 ATP 경쟁적이고 선택적인 CDK1 억제제입니다. Ro-3306은 p53 매개 Bax 활성화 및 미토콘드리아 세포 사멸(mitochondrial apoptosis)을 향상시킵니다.	Cancer Research, May 1, 2018, 2171-2178 Journal of Cell Science, February 13, 2024, jcs261364 Cancer Cell International, December 19, 2024, 409
S1057	Obatoclax Mesylate (GX15-070)	Obatoclax Mesylate (GX15-070)은 무세포 분석에서 0.22 μM의 K_i를 갖는 Bcl-2 길항제이며, MCL-1 매개 Apoptosis 저항성을 극복하는 데 도움을 줄 수 있으며, Autophagy를 유도할 수 있습니다.	Nat Commun, 2025, 16(1):2416 J Transl Med, 2025, 23(1):1262 bioRxiv, 2024, 10.1101/2023.01.18.524628
S7801	A-1331852	A-1331852는 BCL-XL에 대해 0.01 nM 미만의 Ki 값을, Bcl-2, Bcl-W, MCL-1에 대해 각각 6 nM, 4 nM, 142 nM의 Ki 값을 가지는 강력하고 선택적인 BCL-XL 억제제입니다. 이는 암, 면역 질환 및 자가면역 질환 치료에 유용할 수 있습니다.	Br J Cancer, 2026, 134(4):676-684 Cell, 2025, S0092-8674(25)00689-0 Mol Cancer, 2025, 24(1):154
S7790	A-1210477	A-1210477은 MCL-1을 강력하고 선택적으로 억제하는 억제제로, K_i 값은 0.454 nM, IC50 값은 26.2 nM이며, 다른 Bcl-2 계열 단백질에 비해 100배 이상의 선택성을 보입니다.	Front Pharmacol, 2025, 16:1530270 Cell Rep, 2023, 42(10):113176 Int J Mol Sci, 2023, 24(13)11149
S1121	TW-37	TW-37은 무세포 분석에서 각각 0.29 μM, 1.11 μM 및 0.26 μM의 K_i를 갖는 재조합 Bcl-2, Bcl-xL 및 Mcl-1에 대한 새로운 비펩타이드 억제제이며, 이는 Apoptosis를 유도합니다.	Signal Transduct Target Ther, 2025, 10(1):161 bioRxiv, 2024, 10.1101/2023.01.18.524628 Cells, 2023, 12(18)2247
S7800	A-1155463 Dihydrochloride	A-1155463 Dihydrochloride는 매우 강력하고 선택적인 BCL-XL 억제제로, BCL-XL에 대해 피코몰(picomolar) 수준의 결합 친화력을 보이며, BCL-2 및 관련 단백질인 BCL-W(Ki=19 nM)와 MCL-1(Ki>440 nM)에 대해서는 1000배 이상 약한 결합력을 나타냅니다.	Cells, July 2020, 1593 Cell Reports Methods, July 18, 2022, 100256 eLife, December 18, 2018, e40167
1 2

Bcl-2 (B-cell lymphoma 2) is encoded by the Bcl-2 gene and is the first identified member of a large family of apoptosis regulatory proteins (Bcl-2 family) that derives its name from the B-cell lymphoma 2, as it is the second member of a variety of proteins initially described in the t(14;18) chromosomal translocation in human follicular B-cell lymphomas. Bcl-2 contains four Bcl-2 homology domains (BH1-BH4) that mediate the formation of homodimer and heterodimer with relative proteins such as Bax, Bad, Bak and Bcl-xL, and a trans-membrane (TM) domain that mediates insertion into the outer membrane of the mitochondria and the endoplasmic reticulum. Bcl-2 proteins are generally integrated within the outer mitochondrial membrane (OMM), and may also be in the cytosol or ER membrane. The Bcl-2 and other antiapoptotic members of the Bcl-2 family preserve the outer mitochondrial membrane (OMM) integrity, thus inhibiting the mitochondrial signaling pathway of apoptosis, by complex interactions with the proapoptotic Bcl-2 proteins such as Bax, Bak, Bim, Puma and tBid. ^[1][2]

Bcl-2 suppresses apoptosis in response to a broad range of stress stimuli, including those frequently encountered during tumor development, such as oncogene activation, DNA damage, hypoxia (oxygen deprivation), loss of appropriate growth signals and anoikis (loss of cell attachment). In healthy cells, Bax and Bak are kept in check by the pro-survival Bcl-2 family members and the binding of BH3-only proteins unleashes Bax/Bak. Bcl-2 is also critical for the survival of renal epithelial stem cells during embryogenesis, melanocyte progenitors and mature B and T lymphocytes. Bcl-2 over-expression accelerates Eu-myc-induced lymphomagenesis, but loss of endogenous Bcl-2 does not prevent or delay Eu-myc-induced B lymphoma development. Bcl-2 proteins also constitutively binds to Beclin-1, and its dissociation through post-translational modification of Beclin-1 and/or Bcl-2 proteins such as phosphorylation by JNK1, or direct competition for the Bcl-2 BC groove by another BH3-only protein such as Bad, may be sufficient to induce autophagy, leading to the suggestion that autophagy and apoptosis are mechanistically linked. Single-site phosphorylation at Serine 70 (S70) is required for the antiapoptotic function of Bcl-2, and multisite phosphorylation at Threonine 69, S70, and S87 has been reported to inactivate Bcl-2. Phosphorylation of Bcl-2 has been shown to enhance activity to allow response to extracellular growth-factor-mediated signals. ^[1][2][3]

In addition, Bcl-2 is over-expressed in human follicular centre B-cell lymphoma; high levels of Bcl-2 are also detected in significant numbers of chronic lymphocytic leukaemia (CLL), DLBCL and mantle cell lymphoma, as well as in certain solid tumours(brain, breast and lung). The upregulation of Bcl-2 in CLL and other cancers has been attributed to the hypo-methylation of the Bcl-2 promoter or, possibly more importantly due to hemizygous or homozygous loss of the micro RNAs (miRs) 15a and 16-1 that negatively regulate Bcl-2. The dysregulated Bcl-2 proteins in cancer can lead to increased survival of abnormal cells, which are thought to be involved in resistance to conventional cancer treatment. Mice that constitutively express both Myc and Bcl-2 transgenes develop lymphoblastic leukaemia with high incidence, while shut-down of the inducible Bcl-2 transgene in lymphoma-burdened bi-transgenic mice results in tumor regression and significantly prolonged animal survival in many cases, indicating that inactivation of Bcl-2 constitutes a promising new approach to cancer therapy. Small molecule mimetics of BH3-only proteins that can directly target pro-survival Bcl-2 family members are being developed as a novel therapeutic approach. ABT-737 and the closely related orally bioavailable ABT-263, belong to the BH3 mimetic small molecule inhibitors, targeting Bcl-2 and Bcl-2-related proteins such as Bcl-xL and Bcl-w, therefore promoting tumor regression in murine xeno-transplanation models of certain human lymphomas or small cell lung carcinomas and in primary patient-derived follicular lymphoma cells. ^[1][4]