WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406418
CAS#: 226929-39-1
Description: LB42708 is a potent, orally active and selective nonpeptidic farnesyltransferase inhibitor (FTase inhibitor). LB42708 inhibited VEGF-induced Ras activation and subsequently suppressed angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric-oxide synthase pathways in endothelial cells without altering FAK/Src activation.
MedKoo Cat#: 406418
Name: LB42708
CAS#: 226929-39-1
Chemical Formula: C30H27BrN4O2
Exact Mass: 554.1317
Molecular Weight: 555.476
Elemental Analysis: C, 64.87; H, 4.90; Br, 14.39; N, 10.09; O, 5.76
Synonym: LB42708; LB-42708; LB 42708.
IUPAC/Chemical Name: (1-((1-(4-bromobenzyl)-1H-imidazol-5-yl)methyl)-4-(naphthalen-1-yl)-1H-pyrrol-3-yl)(morpholino)methanone
InChi Key: GUUIRIMAQGOLHT-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H27BrN4O2/c31-24-10-8-22(9-11-24)17-35-21-32-16-25(35)18-33-19-28(27-7-3-5-23-4-1-2-6-26(23)27)29(20-33)30(36)34-12-14-37-15-13-34/h1-11,16,19-21H,12-15,17-18H2
SMILES Code: O=C(C1=CN(CC2=CN=CN2CC3=CC=C(Br)C=C3)C=C1C4=C5C=CC=CC5=CC=C4)N6CCOCC6
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | LB42708 is a potent, selective and orally active farnesyltransferase inhibitor. |
| In vitro activity: | Only LB7 induced the upregulation of p21(CIP1/WAF1) and RhoB above the basal level that led to the cell cycle arrest and to distinct morphological alterations of ras-transformed RIE cells. Both FTIs successfully inhibited the ERK and activated JNK in RIE/K-ras cells. Reference: Toxicol Appl Pharmacol. 2006 Sep 15;215(3):317-29. https://pubmed.ncbi.nlm.nih.gov/16712893/ |
| In vivo activity: | LB42708 suppressed tumor growth and tumor angiogenesis in both xenograft tumor models of Ras-mutated HCT116 cells and its wild-type Caco-2 cells, indicating its potential application in the treatment of both Ras-mutated and wild type tumors. Reference: Mol Pharmacol. 2010 Jul;78(1):142-50. https://pubmed.ncbi.nlm.nih.gov/20406854/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 54.01 | |
| DMSO | 65.0 | 117.02 | |
| Ethanol | 58.0 | 104.41 | |
| Ethanol:PBS (pH 7.2) (1:5) | 0.1 | 0.18 |
The following data is based on the product molecular weight 555.476 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Kim CK, Choi YK, Lee H, Ha KS, Won MH, Kwon YG, Kim YM. The farnesyltransferase inhibitor LB42708 suppresses vascular endothelial growth factor-induced angiogenesis by inhibiting ras-dependent mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signal pathways. Mol Pharmacol. 2010 Jul;78(1):142-50. doi: 10.1124/mol.110.063586. Epub 2010 Apr 20. PMID: 20406854. 2. Kim HS, Kim JW, Gang J, Wen J, Koh SS, Koh JS, Chung HH, Song SY. The farnesyltransferase inhibitor, LB42708, inhibits growth and induces apoptosis irreversibly in H-ras and K-ras-transformed rat intestinal epithelial cells. Toxicol Appl Pharmacol. 2006 Sep 15;215(3):317-29. doi: 10.1016/j.taap.2006.03.011. Epub 2006 May 19. PMID: 16712893. 3. Na HJ, Lee SJ, Kang YC, Cho YL, Nam WD, Kim PK, Ha KS, Chung HT, Lee H, Kwon YG, Koh JS, Kim YM. Inhibition of farnesyltransferase prevents collagen-induced arthritis by down-regulation of inflammatory gene expression through suppression of p21(ras)-dependent NF-kappaB activation. J Immunol. 2004 Jul 15;173(2):1276-83. doi: 10.4049/jimmunol.173.2.1276. PMID: 15240720. |
| In vitro protocol: | 1. Kim CK, Choi YK, Lee H, Ha KS, Won MH, Kwon YG, Kim YM. The farnesyltransferase inhibitor LB42708 suppresses vascular endothelial growth factor-induced angiogenesis by inhibiting ras-dependent mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signal pathways. Mol Pharmacol. 2010 Jul;78(1):142-50. doi: 10.1124/mol.110.063586. Epub 2010 Apr 20. PMID: 20406854. 2. Kim HS, Kim JW, Gang J, Wen J, Koh SS, Koh JS, Chung HH, Song SY. The farnesyltransferase inhibitor, LB42708, inhibits growth and induces apoptosis irreversibly in H-ras and K-ras-transformed rat intestinal epithelial cells. Toxicol Appl Pharmacol. 2006 Sep 15;215(3):317-29. doi: 10.1016/j.taap.2006.03.011. Epub 2006 May 19. PMID: 16712893. |
| In vivo protocol: | 1. Kim CK, Choi YK, Lee H, Ha KS, Won MH, Kwon YG, Kim YM. The farnesyltransferase inhibitor LB42708 suppresses vascular endothelial growth factor-induced angiogenesis by inhibiting ras-dependent mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signal pathways. Mol Pharmacol. 2010 Jul;78(1):142-50. doi: 10.1124/mol.110.063586. Epub 2010 Apr 20. PMID: 20406854. 2. Na HJ, Lee SJ, Kang YC, Cho YL, Nam WD, Kim PK, Ha KS, Chung HT, Lee H, Kwon YG, Koh JS, Kim YM. Inhibition of farnesyltransferase prevents collagen-induced arthritis by down-regulation of inflammatory gene expression through suppression of p21(ras)-dependent NF-kappaB activation. J Immunol. 2004 Jul 15;173(2):1276-83. doi: 10.4049/jimmunol.173.2.1276. PMID: 15240720. |
1: Moorthy NS, Sousa SF, Ramos MJ, Fernandes PA. Farnesyltransferase inhibitors: a comprehensive review based on quantitative structural analysis. Curr Med Chem. 2013;20(38):4888-923. PubMed PMID: 24059235.
2: Kim CK, Choi YK, Lee H, Ha KS, Won MH, Kwon YG, Kim YM. The farnesyltransferase inhibitor LB42708 suppresses vascular endothelial growth factor-induced angiogenesis by inhibiting ras-dependent mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signal pathways. Mol Pharmacol. 2010 Jul;78(1):142-50. doi: 10.1124/mol.110.063586. Epub 2010 Apr 20. PubMed PMID: 20406854.
3: Kim HS, Kim JW, Gang J, Wen J, Koh SS, Koh JS, Chung HH, Song SY. The farnesyltransferase inhibitor, LB42708, inhibits growth and induces apoptosis irreversibly in H-ras and K-ras-transformed rat intestinal epithelial cells. Toxicol Appl Pharmacol. 2006 Sep 15;215(3):317-29. Epub 2006 May 19. PubMed PMID: 16712893.
4: Na HJ, Lee SJ, Kang YC, Cho YL, Nam WD, Kim PK, Ha KS, Chung HT, Lee H, Kwon YG, Koh JS, Kim YM. Inhibition of farnesyltransferase prevents collagen-induced arthritis by down-regulation of inflammatory gene expression through suppression of p21(ras)-dependent NF-kappaB activation. J Immunol. 2004 Jul 15;173(2):1276-83. PubMed PMID: 15240720.
5: Kim KW, Chung HH, Chung CW, Kim IK, Miura M, Wang S, Zhu H, Moon KD, Rha GB, Park JH, Jo DG, Woo HN, Song YH, Kim BJ, Yuan J, Jung YK. Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis. Oncogene. 2001 Jan 18;20(3):358-66. PubMed PMID: 11313965.
