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| Targets |
The primary molecular target of Bim BH3, Peptide IV is the hydrophobic groove of anti-apoptotic Bcl-2 family proteins, including Bcl-2, Bcl-xL, Mcl-1, and Bcl-w. These anti-apoptotic proteins sequester pro-apoptotic proteins and prevent cell death. The BH3 domain of Bim binds with high affinity (Ki in the sub-nanomolar range, e.g., 0.5 nM for Bcl-xL) to these hydrophobic grooves. By introducing an exogenous Bim BH3 peptide, the peptide competitively binds to the groove, displacing pro-apoptotic proteins like Bax and Bak. This displacement allows Bax/Bak to oligomerize, permeabilize the mitochondrial outer membrane, and trigger cytochrome c release, activating the caspase cascade leading to apoptosis.
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| ln Vitro |
In vitro, Bim BH3, Peptide IV is a highly potent inducer of apoptosis. As a positive control, it is used to confirm the mechanism of action of small molecule Bcl-2 inhibitors. When added to cell lysates or purified protein systems, it displaces pro-apoptotic proteins from anti-apoptotic proteins. When added to cell cultures (often conjugated to a cell-penetrating peptide), the peptide rapidly induces cell death via the intrinsic mitochondrial apoptotic pathway. Its affinity (Ki) for Bcl-xL is approximately 0.5 nM. The exact EC₅0 for cell death in cancer cell lines varies but is generally in the nanomolar to low micromolar range. The peptide is used to sensitize cancer cells to chemotherapy.
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| ln Vivo |
In vivo, Bim BH3, Peptide IV is rarely used as a standalone therapeutic due to poor stability, rapid clearance, and poor cell penetration. However, stabilized derivatives such as stapled peptides (e.g., SAHB-BIM) have been developed. These stapled peptides have improved proteolytic resistance and cell permeability. In mouse xenograft models of human leukemia (e.g., RS4;11), Bim-based stapled peptides administered intravenously or intraperitoneally have demonstrated anti-tumor activity, leading to tumor growth inhibition and prolonged survival. The native Bim BH3, Peptide IV is primarily used as an in vitro research tool.
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| Enzyme Assay |
A typical non-cellular binding assay is a fluorescence polarization (FP) competition assay. A fluorescently labeled Bim BH3 peptide (e.g., FITC-Bim BH3, 5 nM) is incubated with recombinant anti-apoptotic protein, such as Bcl-xL (5 nM), in assay buffer (50 mM Tris-HCl, pH 7.4, 100 mM NaCl, 1 mM DTT, 0.1% BSA) for 30 min at room temperature. FP is measured (Ex 485/Em 535 nm). For competition, varying concentrations (0.01-1000 nM) of unlabeled Bim BH3, Peptide IV are added, and the decrease in FP is measured. IC₅0 is converted to Ki using the Cheng-Prusoff equation. Ki for Bcl-xL is typically sub-nanomolar.
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| Cell Assay |
A typical in vitro cell-based assay uses human leukemia cell lines such as RS4;11 or HL-60. Cells are cultured in RPMI-1640 with 10% FBS at 37degC, 5% CO2. For cytotoxicity, cells are seeded in 96-well plates at 2 × 10⁴ cells/well. The peptide is often conjugated to a cell-penetrating peptide (e.g., TAT) and added at various concentrations (0.1-10 uM) for 24-48 h. Cell viability is measured using CellTiter-Glo. EC₅0 is calculated. For apoptosis detection, cells are treated with 5 uM peptide for 24 h, stained with Annexin V-FITC and PI, and analyzed by flow cytometry. Caspase-3/9 activation is assessed by Western blotting or fluorogenic substrates.
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| Animal Protocol |
An in vivo study for a stabilized Bim BH3 peptide (e.g., SAHB-BIM) uses a mouse xenograft model of human leukemia. Female NOD/SCID mice (6-8 weeks) are injected intravenously with 5 × 10⁶ RS4;11 cells. One week later, mice are randomized (n=8-10). SAHB-BIM is formulated in saline and administered intravenously at 10, 20, and 40 mg/kg once daily for 14 days. Control receives vehicle. Survival is monitored daily. At study end, mice are euthanized; spleen and bone marrow are harvested to measure leukemic infiltration by flow cytometry (CD45+ cells). Apoptosis in tumor tissue is assessed by TUNEL staining. All procedures require IACUC approval.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of the native Bim BH3, Peptide IV are poor. It has a high molecular weight (3269.65 g/mol), is rapidly degraded by proteases (plasma half-life <30 min), and is cleared renally. It does not readily cross cell membranes. Stabilized analogs (stapled peptides) have improved PK: longer half-life, higher plasma exposure (AUC), and better tissue distribution. Detailed PK data for the native peptide is not typically reported, as it is not a viable drug candidate. Human PK data is not available.
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| Toxicity/Toxicokinetics |
No direct toxicological data is available for Bim BH3, Peptide IV. As an apoptosis-inducing peptide, it is inherently toxic to cells. Systemic toxicity of stabilized Bim BH3 peptides in animals is dose-limiting and can include body weight loss, hepatotoxicity, and effects on the hematopoietic system. On-target toxicity is expected as Bcl-2 proteins are also important for normal cell survival. Standard safety precautions for handling biohazardous materials should be used. For research use only; not for human administration.
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| References |
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| Additional Infomation |
Bim BH3, Peptide IV is not an approved drug. It is a research-grade peptide tool used to study the Bcl-2 family and the intrinsic pathway of apoptosis. Its mechanism involves binding to and neutralizing anti-apoptotic Bcl-2 proteins, leading to activation of apoptosis. The peptide serves as a positive control in assays for small molecule Bcl-2 inhibitors (e.g., ABT-199). Derivatives, such as stapled alpha-helical Bim BH3 peptides, have shown in vivo efficacy, highlighting the potential of such strategies. No clinical trials have been registered for Bim BH3, Peptide IV. For research use only.
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| Molecular Formula |
C145H222N44O41S
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|---|---|
| Molecular Weight |
3269.65
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| Exact Mass |
3268.639
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| CAS # |
721885-31-0
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| Related CAS # |
Bim BH3, Peptide IV TFA
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| PubChem CID |
166603933
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| Appearance |
White to off-white solid powder
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| LogP |
-7.8
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| Hydrogen Bond Donor Count |
51
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| Hydrogen Bond Acceptor Count |
48
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| Rotatable Bond Count |
112
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| Heavy Atom Count |
231
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| Complexity |
7680
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| Defined Atom Stereocenter Count |
28
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| SMILES |
C(C1=CNC2=CC=CC=C12)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(=O)O)CCCNC(N)=N)CC1C=CC(=CC=1)O)CC1C=CC(=CC=1)O)CC1C=CC=CC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(=O)O)NC([C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC(=O)O)=O
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| InChi Key |
FZPOJISTJNAPMH-FDYZCLOZSA-N
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| InChi Code |
InChI=1S/C145H222N44O41S/c1-13-72(6)113(136(225)165-70-107(194)169-103(68-112(203)204)133(222)176-92(47-51-109(197)198)124(213)182-100(62-78-27-17-16-18-28-78)132(221)184-102(67-106(148)193)129(218)167-76(10)118(207)180-99(64-80-39-43-83(191)44-40-80)131(220)183-98(63-79-37-41-82(190)42-38-79)128(217)166-75(9)116(205)170-87(31-21-54-159-141(149)150)121(210)179-96(140(229)230)35-25-58-163-145(157)158)186-126(215)89(33-23-56-161-143(153)154)173-120(209)88(32-22-55-160-142(151)152)174-130(219)97(61-71(4)5)181-123(212)91(46-50-108(195)196)175-122(211)90(45-49-105(147)192)171-117(206)77(11)168-137(226)114(73(7)14-2)188-134(223)101(65-81-69-164-86-30-20-19-29-84(81)86)185-138(227)115(74(8)15-3)187-127(216)93(48-52-110(199)200)177-135(224)104-36-26-59-189(104)139(228)95(34-24-57-162-144(155)156)178-125(214)94(53-60-231-12)172-119(208)85(146)66-111(201)202/h16-20,27-30,37-44,69,71-77,85,87-104,113-115,164,190-191H,13-15,21-26,31-36,45-68,70,146H2,1-12H3,(H2,147,192)(H2,148,193)(H,165,225)(H,166,217)(H,167,218)(H,168,226)(H,169,194)(H,170,205)(H,171,206)(H,172,208)(H,173,209)(H,174,219)(H,175,211)(H,176,222)(H,177,224)(H,178,214)(H,179,210)(H,180,207)(H,181,212)(H,182,213)(H,183,220)(H,184,221)(H,185,227)(H,186,215)(H,187,216)(H,188,223)(H,195,196)(H,197,198)(H,199,200)(H,201,202)(H,203,204)(H,229,230)(H4,149,150,159)(H4,151,152,160)(H4,153,154,161)(H4,155,156,162)(H4,157,158,163)/t72-,73-,74-,75-,76-,77-,85-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,113-,114-,115-/m0/s1
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| Chemical Name |
(4S)-5-[[(2S,3S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3058 mL | 1.5292 mL | 3.0584 mL | |
| 5 mM | 0.0612 mL | 0.3058 mL | 0.6117 mL | |
| 10 mM | 0.0306 mL | 0.1529 mL | 0.3058 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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