WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201761
CAS#: 915412-67-8
Description: LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. LP-261 is a very potent inhibitor of angiogenesis, preventing microvessel outgrowth in the rat aortic ring assay and HUVEC cell proliferation at nanomolar concentrations. Complete inhibition of tumor growth was achieved in the PC3 xenograft model and shown to be schedule dependent. Excellent inhibition of tumor growth in the SW620 model was observed, comparable with paclitaxel. Combining oral, low dose LP-261 with bevacizumab led to significantly improved tumor inhibition. Oral LP-261 is very effective at inhibiting tumor growth in multiple mouse xenograft models and is well tolerated. (source: Invest New Drugs. 2012 Feb;30(1):90-7. doi: 10.1007/s10637-010-9520-5. Epub 2010 Sep 7.)
MedKoo Cat#: 201761
Name: LP-261
CAS#: 915412-67-8
Chemical Formula: C22H19N3O4S
Exact Mass: 421.1096
Molecular Weight: 421.471
Elemental Analysis: C, 62.69; H, 4.54; N, 9.97; O, 15.18; S, 7.61
Synonym: LP-261; LP 261; LP261;
IUPAC/Chemical Name: N-(3-(1H-indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide
InChi Key: YUVDELGTFILMBB-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H19N3O4S/c1-29-21-13-14(6-8-24-21)22(26)16-10-15(11-17(12-16)25-30(2,27)28)18-4-3-5-20-19(18)7-9-23-20/h3-13,23,25H,1-2H3
SMILES Code: CS(=O)(NC1=CC(C(C2=CC=NC(OC)=C2)=O)=CC(C3=CC=CC4=C3C=CN4)=C1)=O
Appearance: Solid powder
Purity: >98%
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: >5 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: | LP-261 is a potent and orally active anti-mitotic agent and shows an inhibition of in vitro tubulin polymerization with an EC50 of 3.2 μM. |
| In vitro activity: | Human umbilical vein endothelial cells (HUVECs) were incubated with LP-261 at 50 nM to 10 μM. LP-261 was found to inhibit HUVEC proliferation in a dose-dependent manner within the tested concentration range of 100 nM to 10 μM, Fig. 2a. Reference: Invest New Drugs. 2012 Feb;30(1):90-7. https://pubmed.ncbi.nlm.nih.gov/20820910/ |
| In vivo activity: | An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model. Reference: J Med Chem. 2011 Jan 13;54(1):179-200. https://pubmed.ncbi.nlm.nih.gov/21126027/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 33.33 | 79.08 |
The following data is based on the product molecular weight 421.471 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. Gardner ER, Kelly M, Springman E, Lee KJ, Li H, Moore W, Figg WD. Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding agent, alone and in combination with bevacizumab. Invest New Drugs. 2012 Feb;30(1):90-7. doi: 10.1007/s10637-010-9520-5. Epub 2010 Sep 7. PMID: 20820910; PMCID: PMC6446042. 2. Shetty RS, Lee Y, Liu B, Husain A, Joseph RW, Lu Y, Nelson D, Mihelcic J, Chao W, Moffett KK, Schumacher A, Flubacher D, Stojanovic A, Bukhtiyarova M, Williams K, Lee KJ, Ochman AR, Saporito MS, Moore WR, Flynn GA, Dorsey BD, Springman EB, Fujimoto T, Kelly MJ. Synthesis and pharmacological evaluation of N-(3-(1H-indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a potent antimitotic agent. J Med Chem. 2011 Jan 13;54(1):179-200. doi: 10.1021/jm100659v. Epub 2010 Dec 2. PMID: 21126027. |
| In vitro protocol: | 1. Gardner ER, Kelly M, Springman E, Lee KJ, Li H, Moore W, Figg WD. Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding agent, alone and in combination with bevacizumab. Invest New Drugs. 2012 Feb;30(1):90-7. doi: 10.1007/s10637-010-9520-5. Epub 2010 Sep 7. PMID: 20820910; PMCID: PMC6446042. |
| In vivo protocol: | 1. Gardner ER, Kelly M, Springman E, Lee KJ, Li H, Moore W, Figg WD. Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding agent, alone and in combination with bevacizumab. Invest New Drugs. 2012 Feb;30(1):90-7. doi: 10.1007/s10637-010-9520-5. Epub 2010 Sep 7. PMID: 20820910; PMCID: PMC6446042. 2. Shetty RS, Lee Y, Liu B, Husain A, Joseph RW, Lu Y, Nelson D, Mihelcic J, Chao W, Moffett KK, Schumacher A, Flubacher D, Stojanovic A, Bukhtiyarova M, Williams K, Lee KJ, Ochman AR, Saporito MS, Moore WR, Flynn GA, Dorsey BD, Springman EB, Fujimoto T, Kelly MJ. Synthesis and pharmacological evaluation of N-(3-(1H-indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a potent antimitotic agent. J Med Chem. 2011 Jan 13;54(1):179-200. doi: 10.1021/jm100659v. Epub 2010 Dec 2. PMID: 21126027. |
1: Shetty RS, Lee Y, Liu B, Husain A, Joseph RW, Lu Y, Nelson D, Mihelcic J, Chao W, Moffett KK, Schumacher A, Flubacher D, Stojanovic A, Bukhtiyarova M, Williams K, Lee KJ, Ochman AR, Saporito MS, Moore WR, Flynn GA, Dorsey BD, Springman EB, Fujimoto T, Kelly MJ. Synthesis and pharmacological evaluation of N-(3-(1H-indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a potent antimitotic agent. J Med Chem. 2011 Jan 13;54(1):179-200. doi: 10.1021/jm100659v. Epub 2010 Dec 2. PubMed PMID: 21126027.
2: Gardner ER, Kelly M, Springman E, Lee KJ, Li H, Moore W, Figg WD. Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding agent, alone and in combination with bevacizumab. Invest New Drugs. 2012 Feb;30(1):90-7. doi: 10.1007/s10637-010-9520-5. Epub 2010 Sep 7. PubMed PMID: 20820910.
3: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):383-408. PubMed PMID: 18806898.
LP-261 is a small-molecule oral drug that has been designed to block tumor growth. The phase I trial was initiated in 2006, was evaluated in patients with hematologic malignancies and advanced solid tumors.
LP-261 is also a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. LP-261 is a very potent inhibitor of angiogenesis, preventing microvessel outgrowth in the rat aortic ring assay and HUVEC cell proliferation at nanomolar concentrations. Complete inhibition of tumor growth was achieved in the PC3 xenograft model and shown to be schedule dependent. Excellent inhibition of tumor growth in the SW620 model was observed, comparable with paclitaxel. Combining oral, low dose LP-261 with bevacizumab led to significantly improved tumor inhibition. Oral LP-261 is very effective at inhibiting tumor growth in multiple mouse xenograft models and is well tolerated.
LP-261, being orally administered and with a novel colchicine binding mode, would offer a new approach to this validated target. In preclinical studies, LP-261 demonstrated broad anti-tumour activity in vitro and, after oral administration, in vivo, including tumour regression in xenograft models of several major solid tumour types. In addition, the compound has demonstrated anti-angiogenic effects in certain angiogenesis models. Importantly, LP-261 has also been shown to be effective in taxol-resistant cells, vinca-resistant cells, and primary leukaemia cells isolated from Gleevec-resistant patients. LP-261 does not appear to be a substrate for MDR pumps. (source: drugresearcher.com).
