ABT-100 free base | A-367074 | CAS#450839-40-4 | Farnesyltransferase inhibitor

MedKoo Cat#: 406416 | Name: ABT-100

Description:

WARNING: This product is for research use only, not for human or veterinary use.

ABT-100 is an orally bioavailable farnesyltransferase inhibitor. ABT-100 inhibited proliferation of cells in vitro carrying oncogenic H-Ras (EJ-1 bladder; IC(50) 2.2 nmol/L), Ki-Ras (DLD-1 colon, MDA-MB-231 breast, HCT-116 colon, and MiaPaCa-2 pancreatic; IC(50) range, 3.8-9.2 nmol/L), and wild-type Ras (PC-3 and DU-145; IC(50), 70 and 818 nmol/L, respectively) as well as clonogenic potential. ABT-100 shows 70% to 80% oral bioavailability in mice. ABT-100 regressed EJ-1 tumors (2-12.5 mg/kg/d s.c., every day for 21 days) and showed significant efficacy in DLD-1, LX-1, MiaPaCa-2, or PC-3 tumor-bearing mice (6.25-50 mg/kg/d s.c. once daily or twice daily orally).

Chemical Structure

ABT-100

CAS#450839-40-4 (free base)

Theoretical Analysis

MedKoo Cat#: 406416

Name: ABT-100

CAS#: 450839-40-4 (free base)

Chemical Formula: C27H19F3N4O3

Exact Mass: 504.1409

Molecular Weight: 504.46

Elemental Analysis: C, 64.28; H, 3.80; F, 11.30; N, 11.11; O, 9.51

Price and Availability

Size	Price	Availability
5mg	USD 190.00	Ready to ship
10mg	USD 350.00	Ready to ship
25mg	USD 750.00	Ready to ship
50mg	USD 1,250.00	Ready to ship
100mg	USD 2,150.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

450839-40-4 (free base) 852926-14-8 (HCl)

Synonym

ABT100; ABT 100; ABT-100; A367074; A 367074; A-367074

IUPAC/Chemical Name

(S)-6-(2-(4-cyanophenyl)-2-hydroxy-2-(1-methyl-1H-imidazol-5-yl)ethoxy)-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carbonitrile

InChi Key

HEUVRFNVTLGKMZ-SANMLTNESA-N

InChi Code

InChI=1S/C27H19F3N4O3/c1-34-17-33-15-25(34)26(35,21-7-2-18(13-31)3-8-21)16-36-24-11-4-19(14-32)12-23(24)20-5-9-22(10-6-20)37-27(28,29)30/h2-12,15,17,35H,16H2,1H3/t26-/m0/s1

SMILES Code

N#CC1=CC(C2=CC=C(OC(F)(F)F)C=C2)=C(OC[C@](O)(C3=CC=C(C#N)C=C3)C4=CN=CN4C)C=C1

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#YMX80227

QC Data

View QC data: current batch, Lot#YMX80227

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ABT-100 is a farnesyltransferase inhibitor that inhibits cell proliferation (IC50s of 2.2 nM, 3.8 nM, 5.9 nM, 6.9 nM, 9.2 nM, 70 nM and 818 nM for EJ-1, DLD-1, MDA-MB-231, HCT-116, MiaPaCa-2, PC-3, and DU-145 cells, respectively).

In vitro activity:

To evaluate the effects of ABT-100 on cell growth, this study used the two liver cancer cell lines, HepG2 and Huh7. Cells were counted after 48 hours of incubation with increasing concentrations of ABT-100 in DMEM with 10% FBS (Fig. 1A) or were treated with ABT-100 (20 μmol/L) and the growth rate was evaluated after 2, 4, and 6 days (Fig. 1B). The growth rate of HepG2 and Huh7 cells treated with ABT-100 was significantly lower in comparison to control cells treated with vehicle alone. These results were further confirmed in a soft agar growth assay (Fig. 1C). Reference: Clin Cancer Res. 2005 Jun 1;11(11):4266-74. https://pubmed.ncbi.nlm.nih.gov/15930366/

In vivo activity:

ABT-100 was given to EJ-1 flank tumor-bearing mice at 12.5 and 6.25 mg/kg/d s.c., every day for 21 days, when the mean tumor volume was 265 mm3. ABT-100 induced regression of these tumors, which was maintained as long as the treatment was continued (Fig. 3A). For the 12.5 and 6.25 mg/kg/d groups, the %ILS values were 223 and 239, respectively (P < 0.001 compared with vehicle-treated groups). In a separate experiment, ABT-100 given at 6.25, 3.125, and 2 mg/kg/d orally twice daily produced similar antitumor activity (data not shown). In addition, ABT-100 given at 12.5, 6.25, and 3.125 s.c., every day for 11 days to scid mice bearing orthotopic EJ-1 bladder xenografts showed dose-dependent reduction in bladder tumor weights. Reference: Clin Cancer Res. 2005 Apr 15;11(8):3045-54. https://pubmed.ncbi.nlm.nih.gov/15930366/

Preparing Stock Solutions

The following data is based on the product molecular weight 504.46 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. Carloni V, Vizzutti F, Pantaleo P. Farnesyltransferase inhibitor, ABT-100, is a potent liver cancer chemopreventive agent. Clin Cancer Res. 2005 Jun 1;11(11):4266-74. doi: 10.1158/1078-0432.CCR-04-2386. PMID: 15930366. 2. Ferguson D, Rodriguez LE, Palma JP, Refici M, Jarvis K, O'Connor J, Sullivan GM, Frost D, Marsh K, Bauch J, Zhang H, Lin NH, Rosenberg S, Sham HL, Joseph IB. Antitumor activity of orally bioavailable farnesyltransferase inhibitor, ABT-100, is mediated by antiproliferative, proapoptotic, and antiangiogenic effects in xenograft models. Clin Cancer Res. 2005 Apr 15;11(8):3045-54. doi: 10.1158/1078-0432.CCR-04-2041. PMID: 15837760. 3. Fong LG, Frost D, Meta M, Qiao X, Yang SH, Coffinier C, Young SG. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science. 2006 Mar 17;311(5767):1621-3. doi: 10.1126/science.1124875. Epub 2006 Feb 16. PMID: 16484451.

In vitro protocol:

In vivo protocol:

1. Fong LG, Frost D, Meta M, Qiao X, Yang SH, Coffinier C, Young SG. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science. 2006 Mar 17;311(5767):1621-3. doi: 10.1126/science.1124875. Epub 2006 Feb 16. PMID: 16484451. 2. Ferguson D, Rodriguez LE, Palma JP, Refici M, Jarvis K, O'Connor J, Sullivan GM, Frost D, Marsh K, Bauch J, Zhang H, Lin NH, Rosenberg S, Sham HL, Joseph IB. Antitumor activity of orally bioavailable farnesyltransferase inhibitor, ABT-100, is mediated by antiproliferative, proapoptotic, and antiangiogenic effects in xenograft models. Clin Cancer Res. 2005 Apr 15;11(8):3045-54. doi: 10.1158/1078-0432.CCR-04-2041. PMID: 15837760.

1: Si MS, Ji P, Lee M, Kwok J, Kusumoto J, Naasz E, Ng SC, Imagawa DK. Potent farnesyltransferase inhibitor ABT-100 abrogates acute allograft rejection. J Heart Lung Transplant. 2005 Sep;24(9):1403-9. doi: 10.1016/j.healun.2004.06.006. PMID: 16143263. 2: Gu WZ, Joseph I, Wang YC, Frost D, Sullivan GM, Wang L, Lin NH, Cohen J, Stoll VS, Jakob CG, Muchmore SW, Harlan JE, Holzman T, Walten KA, Ladror US, Anderson MG, Kroeger P, Rodriguez LE, Jarvis KP, Ferguson D, Marsh K, Ng S, Rosenberg SH, Sham HL, Zhang H. A highly potent and selective farnesyltransferase inhibitor ABT-100 in preclinical studies. Anticancer Drugs. 2005 Nov;16(10):1059-69. doi: 10.1097/00001813-200511000-00004. PMID: 16222147. 3: Ferguson D, Rodriguez LE, Palma JP, Refici M, Jarvis K, O'Connor J, Sullivan GM, Frost D, Marsh K, Bauch J, Zhang H, Lin NH, Rosenberg S, Sham HL, Joseph IB. Antitumor activity of orally bioavailable farnesyltransferase inhibitor, ABT-100, is mediated by antiproliferative, proapoptotic, and antiangiogenic effects in xenograft models. Clin Cancer Res. 2005 Apr 15;11(8):3045-54. doi: 10.1158/1078-0432.CCR-04-2041. PMID: 15837760. 4: Carloni V, Vizzutti F, Pantaleo P. Farnesyltransferase inhibitor, ABT-100, is a potent liver cancer chemopreventive agent. Clin Cancer Res. 2005 Jun 1;11(11):4266-74. doi: 10.1158/1078-0432.CCR-04-2386. PMID: 15930366. 5: Li Z, Zhang Y, Gao Y, Xiang Y, Zhang W, Lu C, Zhuang X. Atipamezole is a promising non-discriminative inhibitor against pan-CYP450 including diclofenac 4'-hydroxylation: A comparison with ABT for drug ADME optimization and mechanism study. Eur J Pharm Sci. 2019 Mar 15;130:156-165. doi: 10.1016/j.ejps.2019.01.010. Epub 2019 Jan 26. PMID: 30690186. 6: Sun Q, Harper TW, Dierks EA, Zhang L, Chang S, Rodrigues AD, Marathe P. 1-Aminobenzotriazole, a known cytochrome P450 inhibitor, is a substrate and inhibitor of N-acetyltransferase. Drug Metab Dispos. 2011 Sep;39(9):1674-9. doi: 10.1124/dmd.111.039834. Epub 2011 Jun 15. PMID: 21677062. 7: Gaylo AE, Laux KS, Batzel EJ, Berg ME, Field KA. Delayed rejection of MHC class II-disparate skin allografts in mice treated with farnesyltransferase inhibitors. Transpl Immunol. 2009 Jan;20(3):163-70. doi: 10.1016/j.trim.2008.09.011. Epub 2008 Oct 18. PMID: 18930822; PMCID: PMC7369389. 8: Fong LG, Frost D, Meta M, Qiao X, Yang SH, Coffinier C, Young SG. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science. 2006 Mar 17;311(5767):1621-3. doi: 10.1126/science.1124875. Epub 2006 Feb 16. PMID: 16484451. 9: Kataoka M, Kojima C, Ueda K, Minami K, Higashino H, Sakuma S, Togashi K, Mutaguchi K, Yamashita S. Quantitative analysis of pharmacokinetic profiles of verapamil and drug-drug interactions induced by a CYP inhibitor using a stable isotope-labeled compound. Drug Metab Pharmacokinet. 2016 Dec;31(6):405-410. doi: 10.1016/j.dmpk.2016.08.001. Epub 2016 Aug 18. PMID: 27876352. 10: Isayama F, Froh M, Bradford BU, McKim SE, Kadiiska MB, Connor HD, Mason RP, Koop DR, Wheeler MD, Arteel GE. The CYP inhibitor 1-aminobenzotriazole does not prevent oxidative stress associated with alcohol-induced liver injury in rats and mice. Free Radic Biol Med. 2003 Dec 15;35(12):1568-81. doi: 10.1016/j.freeradbiomed.2003.09.007. PMID: 14680680. 11: Yang SH, Chang SY, Andres DA, Spielmann HP, Young SG, Fong LG. Assessing the efficacy of protein farnesyltransferase inhibitors in mouse models of progeria. J Lipid Res. 2010 Feb;51(2):400-5. doi: 10.1194/jlr.M002808. Epub 2009 Oct 26. PMID: 19965595; PMCID: PMC2803242. 12: Yang SH, Chang SY, Ren S, Wang Y, Andres DA, Spielmann HP, Fong LG, Young SG. Absence of progeria-like disease phenotypes in knock-in mice expressing a non-farnesylated version of progerin. Hum Mol Genet. 2011 Feb 1;20(3):436-44. doi: 10.1093/hmg/ddq490. Epub 2010 Nov 18. PMID: 21088111; PMCID: PMC3016906. 13: Mathews JM, Raymer JH, Velez GR, Garner CE, Bucher JR. The influence of cytochrome P450 enzyme activity on the composition and quantity of volatile organics in expired breath. Biomarkers. 1996;1(3):196-201. doi: 10.3109/13547509609079357. PMID: 23902325. 14: Henesey CM, Harvison PJ. Renal damage, metabolism and covalent binding following administration of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) to male Fischer 344 rats. Toxicology. 2002 Jan 25;170(3):187-200. doi: 10.1016/s0300-483x(01)00543-1. PMID: 11788156.