Mcl-1
Mcl-1 (myeloid cell leukemia-1) is a critical anti-apoptotic member of the BCL-2 protein family that preserves mitochondrial integrity by restraining the pro-apoptotic effectors BAK and BAX and preventing mitochondrial outer membrane permeabilization (MOMP)[1][2]. Mechanistically, Mcl-1 contains a hydrophobic BH3-binding groove that sequesters pro-apoptotic proteins and suppresses stress-induced apoptosis, thereby maintaining cell survival under physiological and pathological conditions[1][3]. Within the intrinsic apoptotic pathway, BH3-only proteins including NOXA, BIM, PUMA, and BID antagonize anti-apoptotic BCL-2 family members, and NOXA displays notable selectivity toward Mcl-1, promoting apoptotic signaling through Mcl-1 neutralization and degradation[4][5][6]. In cancer models, Mcl-1 overexpression contributes to tumor progression, chemoresistance, and disease relapse, highlighting its role as a major survival factor in malignant cells[7][8]. Compared with related anti-apoptotic isoforms such as BCL-2 and BCL-xL, Mcl-1 exhibits distinct binding preferences and plays a particularly important role in restraining BAK-dependent apoptosis, indicating non-redundant functions within the BCL-2 family network[9][10]. For experimental applications, selective Mcl-1 inhibitors and BH3 mimetics, including MCL-1 SAHB and S63845, disrupt Mcl-1-BAK interactions and induce apoptosis in MCL-1-dependent cancer cells, providing valuable tools for mechanistic studies and therapeutic target validation[11][12].
References:
- [1]. Chipuk JE, et al. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol. 2008 Apr;18(4):157-64. [Content Brief]
- [2]. Willis SN, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005;19(11):1294-1305.
- [3]. Huang K, et al. BH3-only proteins target BCL-xL/MCL-1, not BAX/BAK, to initiate apoptosis. Cell Res. 2019 Nov;29(11):942-952. [Content Brief]
- [4]. Roufayel R, et al. BH3-only proteins Noxa and Puma are key regulators of induced apoptosis. Life (Basel). 2022;12(2):256.
- [5]. Albert MC, et al. CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage. Cell Death Dis. 2020;11:740.
- [6]. Willis SN, et al. Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol. 2005;17(6):617-625.
- [7]. Lee EF, et al. A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation. J Cell Biol. 2008;180(2):341-355.
- [8]. Nakajima W, et al. The anti-apoptotic protein MCL1, a novel target of lung cancer therapy[J]. Journal of Cancer Treatment and Diagnosis, 2018, 2(1).
- [9]. Zhai D, et al. Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family proteins Bcl-B and Mcl-1. J Biol Chem. 2008 Apr 11;283(15):9580-6. [Content Brief]
- [10]. Willis SN, et al. Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol. 2005 Dec;17(6):617-25. [Content Brief]
- [11]. Stewart ML, et al. The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer. Nat Chem Biol. 2010 Aug;6(8):595-601. [Content Brief]
- [12]. Greaves G, et al. BH3-only proteins are dispensable for apoptosis induced by pharmacological inhibition of both MCL-1 and BCL-XL. Cell Death Differ. 2019;26:1037-1047.
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Mcl-1 Related Products (97)
Related Products (97)
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Antibodies (1)
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AF151
0 ImagesCat. No.: HY-174873Purity: 98.87%AF151 is a METTL3 PROTAC degrader with the DC50 of 0.43 μM in MOLM-13 cells. AF151 inhibits cell growth by significantly degrading METTL3 protein and reducing m6A levels. AF151 can induce cell apoptosis and reduce the level of Bcl-2 protein. AF151 can be used for research on cancer such as acute myeloid leukemia (AML). (Pink: METTL3 Ligand (HY-174874); Blue: VHL Ligand (HY-125845); Black: Linker; VHL Ligand+Linker (HY-174875)).
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Mcl1-IN-9
0 ImagesCat. No.: HY-128607CAS No.: 1810769-31-3Mcl1-IN-9 is a potent myeloid cell leukemia-1 (Mcl-1) Inhibitor with an IC50 of 446 nM in reengineered BCR-ABL+ B-ALL cells and a Ki of 0.03 nM.
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A-1210477-piperazinyl
0 ImagesCat. No.: HY-125908CAS No.: 2351218-72-7Synonyms: PROTAC Mcl1-binding moiety 1A-1210477-piperazinyl is a compound binds to protein myeloid cell leukemia 1 (MCL1) used for PROTAC technology.
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E7107
0 ImagesCat. No.: HY-19482CAS No.: 630100-90-2E7107 is a pre-mRNA spliceosome inhibitor and apoptosis (Apoptosis) inducer. E7107 binds to spliceosome-associated protein 130, inhibits spliceosome assembly and pre-mRNA splicing, regulates cellular protein expression, induces G1 and G2/M phase cell cycle arrest, triggers DNA damage, alters R-loop levels, reduces CHEK2 expression, impairs transcriptional elongation, and shifts MCL1 splicing toward pro-apoptotic isoforms. E7107 inhibits tumor growth in xenograft models and reduces leukemia burden. E7107 can be used in the research of advanced solid tumors, acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and triple-negative breast cancer.
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(E)-Mcl-1 inhibitor 7
0 ImagesCat. No.: HY-145825ACAS No.: 2417463-86-4(E)-Mcl-1 inhibitor 7 (Example 34) is a Mcl-1 inhibitor (Ki: <1 nM, IC50: <500 nM). (E)-Mcl-1 inhibitor 7 can be used for research of cancers.
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Mcl-1 inhibitor 3
0 ImagesCat. No.: HY-133015CAS No.: 2376774-73-9Mcl-1 inhibitor 3 (compound 1) is a highly potent and orally activate macrocyclic Mcl-1 inhibitor (Ki= 0.061 nM; IC50=19 nM in an OPM-2 cell viability assay). Mcl-1 inhibitor 3 shows good pharmacokinetic properties and excellent in vivo efficacy without toxicity..
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Mcl-1 inhibitor 12
0 ImagesCat. No.: HY-153423CAS No.: 2445466-24-8Mcl-1 inhibitor 12 (Example 10) is a MCL-1 inhibitor (Ki: 0.22 nM). Mcl-1 inhibitor 12 can be used for the research of cancers.
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Nordentatin
0 ImagesCat. No.: HY-N16746CAS No.: 1083193-15-0Nordentatin is a selective inhibitor targeting GSK-3 with anticancer activity. Nordentatin can inhibit the phosphorylation of GSK-3, downregulate the anti-apoptotic protein Mcl-1 and activate caspase-3 to induce apoptosis (apoptosis). Nordentatin also inhibits the expression of migration-related protein MMP-9 and exerts anti-proliferation and anti-migration activities. Nordentatin is used in research into cancers such as neuroblastoma.
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CDK9-IN-45
0 ImagesCat. No.: HY-179023CDK9-IN-45 (Compound B11) is a highly selective CDK9 inhibitor with IC50 values for CDK9 and CDK1 of 7.13 and 489.5 nM respectively. CDK9-IN-45 exhibits a potent inhibitory effect on colorectal cancer cells. CDK9-IN-45 induces cell apoptosis and leads to significant accumulation of ROS. CDK9-IN-45 activates Caspase-3, downregulates Mcl-1, XIAP, and c-Myc. CDK9-IN-45 can be used for research on colorectal cancer.
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Mcl-1-IN-17
0 ImagesCat. No.: HY-178010Mcl-1-IN-17 (Compound 25) is an orally active Myeloid Cell Leukemia 1 (Mcl-1) inhibitor with a Ki < 0.08 nM. Mcl-1-IN-17 has a significant antiproliferative activity (GI50s of 39 and 105 nM for H929 and A427 cells, respectively) and inhibits cell apoptosis. Mcl-1-IN-17 can be used for hematological and solid cancers research.
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3-Tridecylphenol
0 ImagesCat. No.: HY-N17676CAS No.: 72424-02-33-Tridecylphenol is a cardanol. 3-Tridecylphenol can be isolated from K. hookeriana. 3-Tridecylphenol shows Ki values of >23 μM and >33 μM in BclxL/Bak and Mcl-1/Bid displacement assays, respectively. 3-Tridecylphenol can be used in cancer research.
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ZLMT-72
0 ImagesCat. No.: HY-179633ZLMT-72 is an orally active dual CDK2 and CDK9 inhibitor with IC50s of 0.741 nM and 1.03 nM, respectively. ZLMT-72 shows good selectivity in kinase profiling andcholinesterase inhibition activity. ZLMT-72 has strong antiproliferative effects in the colorectal cancer (CRC) cell line HCT116 (GI50 < 0.1 nM). ZLMT-72 induces apoptosis by inhibiting thephosphorylation of retinoblastoma and RNA polymerase II, resulting in downregulation of antiapoptotic proteins (Mcl-1 and XIAP). ZLMT-72 can be used for the study of colorectal cancer (CRC).
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Mcl-1-IN-16
0 ImagesCat. No.: HY-178008Mcl-1-IN-16 is an effective macrocyclic myeloid cell leukemia 1 (Mcl-1) inhibitor with a Ki of below 0.08 nM. Mcl-1-IN-16 maintains high selectivity (>50,000-fold) for Mcl-1 over other antiapoptotic Bcl-2 family members Bcl-2 and Bcl-xL. Mcl-1-IN-16 leads to the activation of caspase-3/7, thereby initiating cell apoptosis. Mcl-1-IN-16 achieves tumor regression in a lung cancer-derived tumor xenograft mice model. Mcl-1-IN-16 can be used in the research of solid tumor such as nonsmall cell lung cancer (NSCLC).
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Mcl-1-IN-20
0 ImagesCat. No.: HY-178910Mcl-1-IN-20 (Compound 26d) is a Mcl-1 inhibitor with Kis of 0.59, 6.6 and 3.6 μM against Mcl-1, Bcl-xL and Bcl-2. Mcl-1-IN-20 exhibits significant anti-proliferative activity against pancreatic cancer cells and can induce apoptosis in BxPC-3 cells. Mcl-1-IN-20 can be used for the study of pancreatic cancer.
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CDK9 degrader-2
0 ImagesCat. No.: HY-156083CAS No.: 3020773-81-0CDK9 degrader-2 is a bifunctional degrader of ATTEC (Autophagy-Tethering Compound) that degrades the CDK9/cyclin T1 complex. CDK9 degrader-2 forms a ternary complex with CDK9 and LC3B, and achieves degradation through the autophagy-lysosome pathway, a process independent of the ubiquitin-proteasome system. CDK9 degrader-2 downregulates the expression of Mcl-1 and c-Myc proteins, induces apoptosis, and exhibits antitumor activity in in vivo MV4-11 xenograft models. CDK9 degrader-2 can be used for leukemia research.
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8α-Tigloyloxyhirsutinolide 13-O-acetate
0 ImagesCat. No.: HY-138071CAS No.: 83182-58-5Synonyms: 8αTGH8α-Tigloyloxyhirsutinolide 13-O-acetate (8αTGH) is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and pyroptosis, and late DNA damage, cell cycle arrest, apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo.
