For research use only. Not for therapeutic Use.
BIBX-1382 (Cat.No:I002502) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR), a protein that plays a role in cell proliferation and survival. BIBX-1382 has been studied for its potential therapeutic applications in cancer, particularly in non-small cell lung cancer. It has shown to inhibit the growth of cancer cells in preclinical studies. Further research is needed to explore its clinical applications.
| Catalog Number | I002502 |
| CAS Number | 196612-93-8 |
| Synonyms | N8-(3-chloro-4-fluorophenyl)-N2-(1-methylpiperidin-4-yl)pyrimido[5,4-d]pyrimidine-2,8-diamine |
| Molecular Formula | C₁₈H₁₉ClFN₇ |
| Purity | ≥95% |
| Target | Protein Tyrosine Kinase/RTK |
| Solubility | DMSO: ≥ 41 mg/mL |
| Storage | Store at -20°C |
| IC50 | 3 nM [1] |
| IUPAC Name | 4-N-(3-chloro-4-fluorophenyl)-6-N-(1-methylpiperidin-4-yl)pyrimido[5,4-d]pyrimidine-4,6-diamine |
| InChI | InChI=1S/C18H19ClFN7/c1-27-6-4-11(5-7-27)25-18-21-9-15-16(26-18)17(23-10-22-15)24-12-2-3-14(20)13(19)8-12/h2-3,8-11H,4-7H2,1H3,(H,21,25,26)(H,22,23,24) |
| InChIKey | FTFRZXFNZVCRSK-UHFFFAOYSA-N |
| SMILES | N1CCC(CC1)NC2=NC=C3C(=N2)C(=NC=N3)NC4=CC(=C(C=C4)F)Cl |
| Reference | 1:Eur J Cancer. 2002 May;38(8):1072-80. Phase I and pharmacokinetic study of BIBX 1382 BS, an epidermal growth factor receptor (EGFR) inhibitor, given in a continuous daily oral administration.Dittrich Ch,Greim G,Borner M,Weigang-Köhler K,Huisman H,Amelsberg A,Ehret A,Wanders J,Hanauske A,Fumoleau P, PMID: 12008195 </br><span>Abstract:</span> The pyrimido-pyrimidine BIBX 1382 BS inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR), thus specifically reverting the aberrant enzymatic activity from overexpressed and constitutively activated EGFR. A phase I and pharmacokinetic study of this new specific molecule was carried out. After initially performing an accelerated titration design from the first toxicities onwards, a modified Fibonacci scheme was used to escalate the daily oral dose. The following dosages and cycles (defined as treatment during 28 days) were applied: 25 mg: 6; 50 mg: 3; 100 mg: 6; 200 mg: 7; 150 mg: 3. Over a 10 months accrual phase, 11 patients (pts) (7 females, 4 males) with a median age of 63 years (range 50-73 years), World Health Organization Performance Status (WHO PS) 0:5 pts, 1:6 pts and miscellaneous solid tumours were entered. The median number of cycles applied per pt was 2 (range 1-7). Reversible, dose-dependent increase of liver enzymes (maximal Common Toxicity Criteria (CTC) grades: gamma-glutamyl transferase (GGT): 4, aspartate aminotransferase (GOT): 3, alanine aminotransferase (GPT): 3, alkaline phosphatase (AP): 3, bilirubin: 3) occurred. Oral medication yielded plasma levels far below those expected to be efficacious. In conclusion, target plasma levels could not be reached via the oral route at a reasonable dosage. Meanwhile, a preclinically unknown metabolite was identified from the urine of one patient. Subsequently, this metabolite was found to be abundant in patient plasma. The metabolite was demonstrated to be pharmacologically inactive. Due to a dose-limiting increase of liver enzymes, low bioavailability of BIBX 1382 BS and the detection of a pharmacologically inactive metabolite, this trial was discontinued. |
