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Falnidamol (formerly known as BIBX 1382) is a potent and selective inhibitor EGFR inhibitor with IC50 of 3 nM and potential anticancer activities; it displays > 1000-fold lower potency against ErbB2 (IC50 = 3.4 μM) and a range of other related tyrosine kinases (IC50 > 10 μM). BIBX1382 and BIBU1361 are both potent and selective submicromolar inhibitors of the EGFR kinase activity. An IC50 value of 3 nM was determined for both compounds. The potency of these two compounds compares with the one obtained with Iressa, which is a leading EGFR inhibitor in the field. Inhibition of the closest family member, HER2, was 100- to 1000-fold less potent. Furthermore, BIBX1382 and BIBU1361 did not inhibit a number of other related tyrosine kinases.
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Physicochemical Properties
| Molecular Formula |
C18H21CL3FN7
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| Molecular Weight |
460.76
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| Exact Mass |
459.09
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| CAS # |
1216920-18-1
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| Related CAS # |
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| PubChem CID |
46861540
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
479
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C=CC(=C1)NC1C2=C(C=NC(=N2)NC2CCN(C)CC2)N=CN=1)F.Cl.Cl
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| InChi Key |
RFXGEKWBTCMDAW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19ClFN7.2ClH/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);2*1H
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| Chemical Name |
4-N-(3-chloro-4-fluorophenyl)-6-N-(1-methylpiperidin-4-yl)pyrimido[5,4-d]pyrimidine-4,6-diamine;dihydrochloride
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| Synonyms |
| Falnidamol 2HCl;Falnidamol diHCl;BIBX 1382 2HCl;; BIBX1382; BIBX-1382; BIBX 1382BS 2HCl;; BIBX1382BS; BIBX-1382BS |
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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
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| 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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Biological Activity
| ln Vitro |
In vitro activity: Falnidamol (formerly known as BIBX 1382) is a potent and selective inhibitor EGFR inhibitor with IC50 of 3 nM and potential anticancer activities; it displays > 1000-fold lower potency against ErbB2 (IC50 = 3.4 μM) and a range of other related tyrosine kinases (IC50 > 10 μM). BIBX1382 and BIBU1361 are both potent and selective submicromolar inhibitors of the EGFR kinase activity. An IC50 value of 3 nM was determined for both compounds. The potency of these two compounds compares with the one obtained with Iressa, which is a leading EGFR inhibitor in the field. Inhibition of the closest family member, HER2, was 100- to 1000-fold less potent. Furthermore, BIBX1382 and BIBU1361 did not inhibit a number of other related tyrosine kinases.
Kinase Assay: BIBX1382 and BIBU1361 are both potent and selective submicromolar inhibitors of the EGFR kinase activity. An IC50 value of 3 nM was determined for both compounds. The potency of these two compounds compares with the one obtained with Iressa, which is a leading EGFR inhibitor in the field. Inhibition of the closest family member, HER2, was 100- to 1000-fold less potent. Furthermore, BIBX1382 and BIBU1361 did not inhibit a number of other related tyrosine kinases.
Cell Assay: |
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| ln Vivo |
| In nude mice, oral once daily dosing at 10 mg/kg with either BIBX1382 or BIBU1361 completely suppressed tumor growth of human A431 xenografts with respective T/C values of 15 and 6% after 2 weeks of treatment |
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| Animal Protocol |
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| References |
:J Pharmacol Exp Ther.2004 Nov;311(2):502-9. Epub 2004 Jun 15.
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Solubility Data
| Solubility (In Vitro) |
| DMSO:≥ 41 mg/mL | | Water: | | Ethanol: |
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| Solubility (In Vivo) |
| CN1CCC(NC2=NC=C(N=CN=C3NC4=CC=C(F)C(Cl)=C4)C3=N2)CC1.[H]Cl.[H]Cl |
(Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions |
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1 mg |
5 mg |
10 mg |
| 1 mM |
2.1703 mL |
10.8516 mL |
21.7033 mL |
| 5 mM |
0.4341 mL |
2.1703 mL |
4.3407 mL |
| 10 mM |
0.2170 mL |
1.0852 mL |
2.1703 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. |
