Curis Hedgehog and Beyond --plus multi-targeting cancer inhibitors

Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer.

http://pubs.acs.org/doi/full/10.1021/jm901453q

By incorporating histone deacetylase (HDAC) inhibitory functionality into the pharmacophore of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors, we synthesized a novel series of compounds with potent, multiacting HDAC, EGFR, and HER2 inhibition and identified 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide 8 (CUDC-101) as a drug ...

Mol Cancer Ther. 2009 Dec;8(12):3296-306.
Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer.
Bao R, Lai CJ, Wang DG, Qu H, Yin L, Zifcak B, Tao X, Wang J, Atoyan R, Samson M, Forrester J, Xu GX, DellaRocca S, Borek M, Zhai HX, Cai X, Qian C.

Oncology, Curis, Inc., 45 Moulton Street, Cambridge, MA 02138, USA. rbao@curis.com
CUDC-305 is a heat shock ...

CUDC-305 demonstrated high potency in vitro and in vivo across a wide range of cancers. Most notably, Curis scientists observed complete tumor regression following oral administration of CUDC-305 in a mouse xenograft model of acute myelogenous leukemia(AML). Tumor regression has also been observed after treatment of CUDC-305 in mouse xenograft models of breast, non-small cell lung, gastric cancer and glioblastoma brain cancers. In this preclinical testing, the compound also demonstrated an ability to effectively cross ...

CUDC-101 is a molecule that can target 3 different and novel cancer pathways at once. This allows patients to take a single doses instead of having to take multiple agents at once or at various times. The intent of this design is for network disruption.

• Efficacy dose ranges are above 150mg/m2
• About double the half life in tumors when compared to plasma

What does CUDC-101 Target? (EGFR, HDAC, HER2)

EGFR (Epidermal growth factor receptor) ...