MedKoo product information:

LP-261

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).

Current developer:    Locus Pharmaceuticals

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2. Kelly, Martha; Lee, Younghee; Liu, Bin; Fujimoto, Ted; Freundlich, Joel; Dorsey, Bruce D.; Flynn, Gary A.; Husain, Arifa; Moore, William R., Jr. Preparation of heterocyclic anticancer agents and uses thereof. U.S. Pat. Appl. Publ. (2008), 81pp. CODEN: USXXCO US 2008280891 A1 20081113 CAN 149:556450 AN 2008:1367859 CAPLUS.

3: 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. 2010 Sep 7. [Epub ahead of print] PubMed PMID: 20820910.

4: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):383-408. PubMed PMID: 18806898.