| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
BMS‑214662 targets farnesyl transferase (FTase), inhibiting the post‑translational farnesylation of proteins such as Ras, thereby disrupting signal transduction. It is highly selective for FTase (IC50 1.3 nM) over GGTase (IC50 1.9 μM), minimising off‑target effects on geranylgeranylated proteins.
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| ln Vitro |
BMS-214662 has over 1000-fold selectivity for farnesyl transferase, as evidenced by its IC50 values of 1.3 and 2.3 μM for geranylgeranylation inhibition of K-Ras and Ras-CVLL, respectively [1]. BMS-214662 shown good efficiency in suppressing human colon cancer tumor cells HCT-116, human ovarian cancer tumor cells A2780, and H-ras-transformed mouse cells. The most effective apoptotic FTI now available is BMS-214662, which has strong, yet broad-spectrum, cytotoxic activity against a variety of cell lines with different histologies [2].
In vitro, BMS‑214662 induces apoptosis in chronic myeloid leukaemia stem/progenitor cells (including CD34+38‑) at 250 nM for 24 hours, via protein kinase C beta activation and mitochondrial apoptosis. It shows potent antiproliferative activity against various tumour cell lines. |
| ln Vivo |
Compared to untreated control mice, BMS-214662-treated mice's tumors included a higher quantity of apoptotic cells. When compared to untreated controls, AI in HCT-116 tumors of mice treated with BMS-214662 rose 4–10 times. BMS-214662 exhibits noteworthy cytotoxicity against HCT-116 and EJ-1 tumor cells. It has been observed that for HCT-116 and EJ-1 tumors, respective dosages of 75 and 100 mg/kg are necessary to eradicate 90% of clonal tumor cells.
In vivo, BMS‑214662 induces tumour cell apoptosis in HCT‑116 xenograft‑bearing mice at doses of 250 mg/kg (i.v.) or 300‑400 mg/kg (p.o.); doses required to kill 90% of clonogenic cells are ~75 mg/kg for HCT‑116 and 100 mg/kg for EJ‑1 tumours, confirming robust antitumour efficacy. |
| Enzyme Assay |
FTase inhibitory activity is measured in cell‑free assays using recombinant FTase, a biotinylated Ras peptide substrate, and [³H]farnesyl pyrophosphate; incorporation of radiolabel is quantified, and IC50 is derived. Selectivity over GGTase is assessed using similar assays with geranylgeranyl substrate.
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| Cell Assay |
Cell‑based assays use cancer cell lines (e.g., CML, HCT‑116); apoptosis is measured by mitochondrial membrane potential, caspase activation, or Annexin V staining after treatment with BMS‑214662 at 250 nM for 24 hours. Cell viability and proliferation are assessed by MTT or cell counting.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models; BMS‑214662 is administered intravenously (250 mg/kg) or orally (300‑400 mg/kg). Tumour growth inhibition and apoptosis induction are assessed by histology and TUNEL staining. PK/PD relationships are also explored.
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| ADME/Pharmacokinetics |
BMS‑214662 is soluble in DMSO (80 mg/mL) and practically insoluble in water. It has been given i.v. and p.o. in animal studies. Detailed half‑life, bioavailability, and metabolism are not fully disclosed, but its oral activity suggests reasonable absorption.
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| Toxicity/Toxicokinetics |
No detailed toxicology data are published; however, as an FTI, potential toxicities include gastrointestinal, haematological, and hepatic effects. Its clinical development may have been limited by toxicity or PK issues, but preclinical safety at effective doses appears manageable.
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| References |
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| Additional Infomation |
BMS-214662 is a benzodiazepine compound with the structure 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine, substituted at positions 1, 3R, 4, and 7 with (1H-imidazol-5-yl)methyl, benzyl, (thien-2-yl)sulfonyl, and cyano groups, respectively. It is a potent farnesyltransferase inhibitor (IC50 = 1.35 nM) and has been clinically developed for the treatment of solid tumors. It exhibits antitumor activity, apoptosis-inducing activity, and EC 2.5.1.58 (protein farnesyltransferase) inhibitory activity. It belongs to the imidazole, nitrile, thiophene, sulfonamide, benzene, and benzodiazepine classes of compounds. BMS-214662 has been used in clinical trials for the treatment of childhood myelodysplastic syndromes, refractory anemia with blasts, relapsed adult acute myeloid leukemia, relapsed chronic myeloid leukemia, and adult acute promyelocytic leukemia (M3). BMS-214662 is a non-sedating benzodiazepine derivative with potential antitumor activity. The farnesyltransferase inhibitor BMS-214662 inhibits farnesyltransferase and its post-translational farnesylation modification of various proteins involved in signal transduction, thereby inhibiting Ras function and inducing apoptosis in susceptible tumor cells. This drug may reverse the malignant phenotype of H-Ras-transformed cells and has been shown to be effective against tumor cells with and without Ras mutations.
BMS‑214662 is an investigational anticancer agent not approved; it has shown preclinical activity in Ras‑driven tumours and AML. Its potent FTase inhibition and apoptosis induction make it a candidate, but further development requires improved PK and safety profiles. |
| Molecular Formula |
C25H23N5O2S2
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|---|---|
| Molecular Weight |
489.61242
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| Exact Mass |
489.129
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| CAS # |
195987-41-8
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| PubChem CID |
448545
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| Appearance |
White to off-white solid powder
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| Density |
1.45g/cm3
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| Boiling Point |
790.9ºC at 760mmHg
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| Flash Point |
432.1ºC
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| Vapour Pressure |
5.38E-25mmHg at 25°C
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| Index of Refraction |
1.722
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
834
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N#CC1=CC=C(N(CC2=CN=CN2)C[C@@H](CC3=CC=CC=C3)N(S(=O)(C4=CC=CS4)=O)C5)C5=C1
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| InChi Key |
OLCWFLWEHWLBTO-HSZRJFAPSA-N
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| InChi Code |
InChI=1S/C25H23N5O2S2/c26-13-20-8-9-24-21(11-20)15-30(34(31,32)25-7-4-10-33-25)23(12-19-5-2-1-3-6-19)17-29(24)16-22-14-27-18-28-22/h1-11,14,18,23H,12,15-17H2,(H,27,28)/t23-/m1/s1
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| Chemical Name |
(3R)-3-benzyl-1-(1H-imidazol-5-ylmethyl)-4-thiophen-2-ylsulfonyl-3,5-dihydro-2H-1,4-benzodiazepine-7-carbonitrile
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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 |
| 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) |
DMSO : ≥ 100 mg/mL (~204.24 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0424 mL | 10.2122 mL | 20.4244 mL | |
| 5 mM | 0.4085 mL | 2.0424 mL | 4.0849 mL | |
| 10 mM | 0.2042 mL | 1.0212 mL | 2.0424 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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