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| 5mg |
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| 10mg |
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| 25mg |
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HhAntag is a novel and potent GLI1-mediated transcription inhibitor and SMO antagonist with anticancer activity. It inhibits GLI1-mediated transcription, which is an essential down-stream element of the Hedgehog (Hh) pathway.
| ln Vitro |
HhAntag (2-30 µM; 72 hours) inhibits Hh signaling pathway-sensitive cells with IC50 values ranging from 2 µM to >30 µM[1]. It is ten times more powerful than the natural product SMO antagonist cyclopamine in suppressing Hh pathway activity. With IC50 values of 30 µM, 5.4 µM, and 5.8 µM, HhAntag inhibits AsPC-1, BXPC-3, CFPAC, HPAC, HPAF-II, KP4, Panc 03.27, PA-TU-8902, PSN-1, and SU.86.86 cells. These are 2.7 µM, 6.2 µM, 10.3 µM, 2.5 µM, 2.9 µM, 5.8 µM, and 2.7 µM[1]. A Hh-responsive human mesenchymal cell line (HEPM) expressing GLI luciferase reporter construct (HEPM-rep) requires 100 nM of HhAntag to completely inhibit Hh signaling; this is greater than the value required for inhibition, which is 400 times lower, and in the most sensitive cancer cell line (1.9 μM), cell growth increases by 50% [1].
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| ln Vivo |
In HT55 and HT-29 colorectal cell line xenograft models, HhAntag (oral treatment; 75 mg/kg or 100 mg/kg; twice daily; 25 days) significantly slowed tumor growth, with an average tumor growth inhibition rate of 29% and 48%, respectively. DLD-1 xenograft development is unaffected by HhAntag [1].
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| Animal Protocol |
Animal/Disease Models: Primary human xenografts (DLD-1, HT55 and HT-29 cells) from 6-8 week old female CD1 nu/nu (nude) mice [1]
Doses: 75 mg/kg or 100 mg/kg twice (two times) daily ; 25-day Experimental Results: Caused growth delay in HT55 and HT-29 xenografts, but had no effect on DLD-1 xenografts. |
| References |
[1]. Neeraj Mahindroo, et al. Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway. Bioorg Med Chem. 2010 Jul 1;18(13):4801-11.
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| Molecular Formula |
C24H23CLN4O3
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|---|---|
| Molecular Weight |
450.92
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| Exact Mass |
450.1459
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| CAS # |
496794-70-8
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| SMILES |
O=C(NC1=CC=C(Cl)C(C2=NC3=CC=C(N(C)C)C=C3N2)=C1)C4=CC(OC)=CC(OC)=C4
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| Synonyms |
Hh Antag Hh-Antag HhAntag
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~221.77 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (6.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (6.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2177 mL | 11.0884 mL | 22.1769 mL | |
| 5 mM | 0.4435 mL | 2.2177 mL | 4.4354 mL | |
| 10 mM | 0.2218 mL | 1.1088 mL | 2.2177 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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