TAK-441 (Synonyms: TAK441;TAK-441) |
Catalog No.GC20158
One-Click Copy Product Info
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TAK-441 is a highly potent and orally bioavailable synthetic small molecule Smoothened (Smo) antagonist.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1186231-83-3
Sample solution is provided at 25 µL, 10mM.
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TAK-441 is a highly potent and orally bioavailable synthetic small molecule Smoothened (Smo) antagonist. It has an IC50 of 4.6 nM evaluated using luciferase reporter activities in NIH3T3 cells carrying a stably transfected Gli-reporter construct [1]. TAK-441 exhibits high potency and oral bioavailability as an inhibitor of hedgehog (Hh) signaling, with an IC50 value of 4.4 nM [2]. TAK-441 has strong antitumor activity in solid tumors [1].
TAK-441 (48 h) inhibits Gli1 mRNA with IC50 values of 0.0457 and 0.113 mg/ml in the tumor and skin, respectively [2].
TAK-441(25 mg/kg/d, 8 weeks, oral) treated LNCaP cells xenograft mice tumor volumes were approximately one-third of vehicle control [3].TAK-441 treated average tumor growth rate of Ptc1+/- p53-/- medulloblastoma allograft model in mice at 10 mg/kg and 25 mg/kg was 16% and 9% of vehicle-treated mice [1].TAK-441 showed favorable oral bioavailability (F), which was 32% in rats and 90% in dogs [2].
References:
[1]. Ibuki N, Ghaffari M, Pandey M, Iu I, Fazli L, Kashiwagi M, Tojo H, Nakanishi O, Gleave ME, Cox ME. TAK‐441, a novel investigational smoothened antagonist, delays castration‐resistant progression in prostate cancer by disrupting paracrine hedgehog signaling. International journal of cancer. 2013 Oct 15;133(8):1955-66.
[2]. Ohashi T, Oguro Y, Tanaka T, Shiokawa Z, Tanaka Y, Shibata S, Sato Y, Yamakawa H, Hattori H, Yamamoto Y, Kondo S. Discovery of the investigational drug TAK-441, a pyrrolo [3, 2-c] pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: Modification of the core skeleton for improved solubility. Bioorganic & medicinal chemistry. 2012 Sep 15;20(18):5507-17.
[3]. Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S. Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment. International journal of cancer. 2017 Jan 15;140(2):358-69.
| Animal experiment [2]: | |
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Animal models |
6-8-week old male athymic nude mice (Harlan Sprague-Dawley) |
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Preparation Method |
2 × 106 LNCaP cells were suspended in 0.1 mL Matrigel and inoculated s.c. in the flank of 6-8-week old male athymic nude mice via a 27-gauge needle under isoflurane anesthesia as previously described.13 Gonadally intact animals harboring xenografts that grew to >150 mm3 with circulating PSA levels of >100 ng/mL between 4 and 6 weeks of inoculation were castrated and randomized to vehicle or 25 mg/kg TAK-441, orally treated once daily for 8 weeks. Each experimental group consisted of eight mice. |
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Dosage form |
25 mg/kg/d, oral, for 8 weeks. |
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Applications |
25 mg/kg TAK-441 treated mice tumor volumes at sacrifice being approximately one-third of vehicle control. |
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References: [1]: Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, Cox ME, Li N, Guns ES, Yenki P, Pham S. Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment. International journal of cancer. 2017 Jan 15;140(2):358-69. |
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| Cas No. | 1186231-83-3 | SDF | |
| Synonymes | TAK441;TAK-441 | ||
| Formula | C28H31F3N4O6 | M.Wt | 576.56 |
| Solubility | DMSO:Soluble; H2O:Insoluble | Storage | Powder: -20°C for 3 years; In solvent: -80°C for 2 years |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7344 mL | 8.6721 mL | 17.3442 mL |
| 5 mM | 346.9 μL | 1.7344 mL | 3.4688 mL |
| 10 mM | 173.4 μL | 867.2 μL | 1.7344 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: 98.79% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)