HPI 1 - CAS 599150-20-6
Category: Inhibitor
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HPI 1 is a hedgehog (Hh) signaling inhibitor that blocks Sonic hedgehog (Shh)-, SAG- and Gli-induced Hh pathway activation in Shh-LIGHT2 cells (IC50 = 1.5, 1.5, 4 and 6 μM for Shh-, SAG-, Gli2- and Gli1-induced activation) with no effect on Wnt signaling. HPI 1 also inhibits Hh pathway activation in SmoM2-LIGHT cells (IC50 = 2.5 μM), and prevents the proliferation of cerebellar granule neuron precursors expressing SmoM2.
Brife Description:
hedgehog (Hh) signaling inhibitor
≥95% by HPLC
HPI 1; HPI1; HPI-1; 1,4,5,6,7,8-Hexahydro-4-(3-hydroxyphenyl)-7-(2-methoxyphenyl)-2-methyl-5-oxo-3-quinolinecarboxylic acid 2-methoxyethyl ester
Canonical SMILES:
1.Polymeric nanoparticle-encapsulated hedgehog pathway inhibitor HPI-1 (NanoHHI) inhibits systemic metastases in an orthotopic model of human hepatocellular carcinoma.
Xu Y;Chenna V;Hu C;Sun HX;Khan M;Bai H;Yang XR;Zhu QF;Sun YF;Maitra A;Fan J;Anders RA Clin Cancer Res. 2012 Mar 1;18(5):1291-302. doi: 10.1158/1078-0432.CCR-11-0950. Epub 2011 Aug 25.
PURPOSE: ;To illustrate the prognostic significance of hedgehog (Hh) signaling in patients with hepatocellular carcinoma (HCC) and to evaluate the efficacy of a novel nanoparticle-encapsulated inhibitor of the Hh transcription factor, Gli1 (NanoHHI) using in vitro and in vivo models of human HCCs.;EXPERIMENTAL DESIGN: ;Patched1 (Ptch1) expression was detected in tumor tissue microarrays of 396 patients with HCC who underwent curative surgical resection during February 2000 to December 2002. Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. The effects of NanoHHI alone and in combination with sorafenib were investigated on HCC cell lines. Primary HCC tumor growth and metastasis were examined in vivo using subcutaneous and orthotopic HCC xenografts in nude mice.;RESULTS: ;Elevated expression of Ptch1 in HCC tissues was significantly related to disease recurrence, as well as a shorter time to recurrence in patients with HCC. In vitro, NanoHHI significantly inhibited the proliferation and invasion of HCC cell lines. NanoHHI potently suppressed in vivo tumor growth of HCC xenografts in both subcutaneous and orthotopic milieus, and in contrast to sorafenib, resulted in significant attenuation of systemic metastases in the orthotopic setting.
2.Metabolism of tetramethrin isomers in rat: IV. Tissues responsible for formation of reduced and hydrated metabolites.
Tomigahara Y;Onogi M;Saito K;Kaneko H;Nakatsuka I;Yamane S Xenobiotica. 1997 Sep;27(9):961-71.
1. To identify the sites of formation of the reduced metabolites, 3-hydroxy-cyclohexane-1,2-dicarboximide (3-OH-HPI-1 and -2), 1,2-cyclohexanedicarboxylic acid (TCDA) and 1-hydroxy-1,2-cyclohexanedicarboxylic acid (1-OH-HPA), in rat treated with 14C-labelled (1RS, trans)-tetramethrin, [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate], bile-duct cannulated animals were orally or intravenously administered 14C-labelled 3,4,5,6-tetrahydrophthalimide (TPI) or 3,4,5,6-tetrahydrophthalic acid (THPA), precursors of these metabolites, and bile, urine and faeces were collected for analysis. 2. 3-OH-HPI-1 and 3-OH-HPI-2, which are cis-form reduced metabolites, and 1-OH-HPA were detected in bile and urine samples of the bile-cannulated rat treated intravenously and orally with 14C-labelled TPI, indicating their formation in tissues or blood. TCDA, a trans-form reduced metabolite, was not detected in bile, urine or faeces of the bile-cannulated rat treated intravenously with 14C-THPA, but was found in the faeces after oral application, indicating formation in the gastrointestinal tract. 3. To clarify whether 1-OH-HPA is produced from THPA via TCDA (hydroxylation via reduction) or by direct addition of H2O to its double bond (hydration), rats were orally administered 14C-labelled TCDA, and metabolites in urine and faeces were analysed.
3.Metabolism of tetramethrin isomers in rat. III. Stereochemistry of reduced metabolites.
Tomigahara Y;Onogi M;Miki M;Yanagi K;Shiba K;Kaneko H;Nakatsuka I;Yamada H Xenobiotica. 1996 Feb;26(2):201-10.
1. Three main urinary metabolites, two isomers of 3-hydroxycyclohexane-1,2-dicarboximide (3-OH-HPI-1 and 2) and 1,2-tetrahydrodicarboxylic acid (TCDA) were purified from rat treated with (1RS, trans)-tetramethrin [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate]. 2. To elucidate the mechanism of formation of these reduced metabolites, the stereochemistry of 3-OH-HPI-1, 3-OH-HPI-2 and TCDA was clarified by chemical reactions, spectroanalysis (nmr) and X-ray analysis. 3. The sole difference in configuration between 3-OH-HPI-1 and 3-OH-HPI-2 was found to be the orientation of the hydroxyl group to the cyclohexane ring, and both of these reduced metabolites showed cis-addition of two hydrogens. In contrast, reduction resulted in the trans form with TCDA. 4. These findings indicate the existence of two different reduction reaction mechanisms in the rat.
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CAS 599150-20-6 HPI 1

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