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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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.
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CPA-7
0 ImagesCat. No.: HY-122759CAS No.: 16961-77-6CPA7 is a novel Stat3 inhibitor. CPA7 downregulates survivin, Bcl-XL, and Mcl-1. CPA7 induces Apoptosis. CPA7 enhances the radiosensitivity of prostate cancer. CPA7 has anti-cancer effects against prostate cancer.
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A09-003
0 ImagesCat. No.: HY-155245CAS No.: 2911646-14-3
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Bcl-2/Mcl-1-IN-5
0 ImagesCat. No.: HY-181746Bcl-2/Mcl-1-IN-5 (Compound S6) is a Bcl-2 and Mcl-1 inhibitor. Bcl-2/Mcl-1-IN-5 promotes Apoptosis, downregulates anti-apoptotic proteins Bcl-2 and Mcl-1, induces mitochondrial membrane potential depolarization, and activates the Caspase-dependent apoptotic cascade, as evidenced by Caspase-3 activation and PARP1 cleavage. Bcl-2/Mcl-1-IN-5 has anti-hepatocellular carcinoma activity.
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JNJ-4355
0 ImagesCat. No.: HY-150507CAS No.: 2697112-33-5Synonyms: JNJ-78394355JNJ-4355, a chemical probe, is a highly potent MCL-1 (myeloid cell leukemia-1) inhibitor, with KI of 18 pM. JNJ-4355 shows antitumor activity.
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Cyclocommunol
0 ImagesCat. No.: HY-N3665CAS No.: 145643-96-5Cyclocommunol is a GST inhibitor with an IC50 of 3.0 μM. Cyclocommunol downregulates the expression of the anti-apoptotic (apoptosis) protein Mcl-1, reduces the levels of phosphorylated Akt and mTOR, and induces caspase-dependent apoptosis, reactive oxygen species (ROS) production and autophagy. Cyclocommunol can be used in research related to oral squamous cell carcinoma, breast cancer, lung cancer, norovirus-induced gastroenteritis and bacterial infections.
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Mcl1 Degrader-1
0 ImagesCat. No.: HY-184160Mcl1 Degrader-1 is an autophagy-targeting chimera (AUTAC) that selectively degrades the Mcl1 protein. Mcl1 Degrader-1 mediates K63 ubiquitination of Mcl1 via TRAF6/UBC13, transports it to autolysosomes for degradation through p62/SQSTM1, and activates Beclin1-dependent autophagy. Mcl1 Degrader-1 can be used in studies related to multiple myeloma and non-small cell lung cancer.
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MLS-2384 free base
0 ImagesCat. No.: HY-125718CAS No.: 1067884-45-0MLS-2384 free base is a dual JAK/Src kinase inhibitor. MLS-2384 free base downregulates STAT3 downstream proteins c-Myc and Mcl-1. MLS-2384 free base induces Apoptosis. MLS-2384 free base exhibits anticancer activity against prostate cancer, breast cancer, skin cancer, ovarian cancer, lung cancer, and liver cancer.
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Mcl-1-IN-21
0 ImagesCat. No.: HY-181054Mcl-1-IN-21 is a selective Mcl-1 protein inhibitor. Mcl-1-IN-21 can induce apoptosis, elevate intracellular ROS, reduce mitochondrial membrane potential, exert cytotoxicity against human cervical cancer cells, and inhibit tumor growth in a human cervical cancer xenograft mouse model. Mcl-1-IN-21 can be used for the research of cervical cancer.
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Mcl-1 inhibitor 13
0 ImagesCat. No.: HY-153423ACAS No.: 2445466-06-6Mcl-1 inhibitor 13 (Example 9) is a MCL-1 inhibitor (Ki: 8.2 nM). Mcl-1 inhibitor 13 can be used for the research of cancers.
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Mcl-1-IN-22 hydrochloride
0 ImagesCat. No.: HY-183601AMcl-1-IN-22 hydrochloride is a tetrahydro-β-carboline-based Mcl-1 inhibitor with a Ki of 0.015 μM. Mcl-1-IN-22 hydrochloride shows antitumor activity, induces apoptosis and produces synergistic antitumor effects in combination with Cisplatin (HY-17394) and Paclitaxel (HY-B0015). Mcl-1-IN-22 hydrochloride can be used for the research of cancer, such as ovarian cancer.
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PROTAC HDAC3 degrader-1
0 ImagesCat. No.: HY-181767CAS No.: 3133883-15-2PROTAC HDAC3 degrader-1 is a selective PROTAC degrader targeting HDAC3 with a DC50 of 30.73 nM. PROTAC HDAC3 degrader-1 induces degradation of HDAC3 via the ubiquitin-proteasome system. PROTAC HDAC3 degrader-1 promotes apoptosis, induces DNA damage, and downregulates anti-apoptotic proteins Mcl-1 and Bcl-xL. PROTAC HDAC3 degrader-1 can be used for the research of acute myeloid leukemia.
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CDK9/CycT1 degrader-1
0 ImagesCat. No.: HY-156795CAS No.: 3020773-91-2CDK9/CycT1 degrader-1 is an autophagy-anchored bifunctional degrader that mediates the degradation of the CDK9/cyclin T1 protein complex. CDK9/CycT1 degrader-1 binds both CDK9 and LC3B simultaneously to form a ternary complex, achieving target protein degradation via the autophagy-lysosome pathway. CDK9/CycT1 degrader-1 downregulates the protein levels of Mcl‑1 and c‑Myc and induces apoptosis. PROTAC CDK9/CycT1 Degrader-2 is applicable to cancer-related research.
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W1307
0 ImagesCat. No.: HY-184891CAS No.: 3028770-95-5W1307 is a selective STAT3 inhibitor with a KD value of 1.74 μM. W1307 inhibits STAT3 Tyr705 phosphorylation, disrupts STAT3 dimerization, and suppresses STAT3 transcriptional activity. W1307 downregulates the expression of STAT3 downstream targets c-Myc, Mcl-1 and Bcl-2. W1307 transcriptionally inhibits SREBP1 and CPT2 expression to disrupt lipid homeostasis. W1307 shows potent anti-leukemic activity and synergizes with Cytarabine (Ara-C) (HY-13605) to overcome chemoresistance in acute myeloid leukemia (AML).
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Mcl-1-IN-23
0 ImagesCat. No.: HY-184310CAS No.: 2756736-34-0Mcl-1-IN-23 is a Mcl-1 inhibitor with a Ki value of 0.024 μM. Mcl-1-IN-23 binds directly to Mcl-1 and displaces the pro-apoptotic proteins Bak and Bim from Mcl-1 complexes. Mcl-1-IN-23 induces cell apoptosis, activates caspase-3, promotes PARP cleavage, and exerts antiproliferative activity against cancer cells. Mcl-1-IN-23 can be used for the research of leukemia.
