WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406440
CAS#: 1453097-13-6
Description: HUHS015 is a potent PCA-1/ALKBH3 inhibitor both in vitro and in vivo. The bioavailability (BA) of HUHS015 was 7.2% in rats after oral administration. As expected, continuously administering HUHS015 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.
Hodoodo Cat#: H406440
Name: HUHS015
CAS#: 1453097-13-6
Chemical Formula: C19H18N4O
Exact Mass: 318.15
Molecular Weight: 318.372
Elemental Analysis: C, 71.68; H, 5.70; N, 17.60; O, 5.03
Synonym: HUHS015; HUHS 015; HUHS-015
IUPAC/Chemical Name: 4-benzyl-3-methyl-1-(5-methyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-5-ol.
InChi Key: LFEFEOLVKXXVGD-UHFFFAOYSA-N
InChi Code: InChI=1S/C19H18N4O/c1-12-8-9-16-17(10-12)21-19(20-16)23-18(24)15(13(2)22-23)11-14-6-4-3-5-7-14/h3-10,24H,11H2,1-2H3,(H,20,21)
SMILES Code: OC1=C(CC2=CC=CC=C2)C(C)=NN1C3=NC4=CC(C)=CC=C4N3
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | HUHS015 is a potent prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitor with an IC50 of 0.67μM for PCA-1. |
| In vitro activity: | Compounds with weak PCA-1/ALKBH3 inhibitory activity, such as 12, demonstrated weak proliferation inhibition against DU145, while those with sub-micromolar IC50 values, such as 15, 35 (HUHS015), 38, and 49, exhibited more potent effects. Consequently, 35 (HUHS015) was selected for further studies because it exhibited an adequate level of serum concentration after oral administration and potent inhibition during both the enzymatic and cell assays. Reference: Bioorg Med Chem Lett. 2014 Feb 15;24(4):1071-4. https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(14)00027-4 |
| In vivo activity: | The preliminary bioavailability (BA) value for 35 (HUHS015) was measured after oral administration to rats, revealing a 7.2% BA value (Figs. S1 and S2). This BA value was sufficient for continuing the in vivo studies. The growth inhibition demonstrated by 35 (32 mg/kg) was examined in a mouse xenograft model bearing DU145 after subcutaneous injection (Fig. 2); potent growth inhibition was observed without limiting weight gains, even after a 6-day continuous administration. Therefore, the synthesizing small molecule inhibitor of PCA-1/ALKBH3, a clinically identified novel target, demonstrated promising results for developing an anti-prostate cancer drug without mechanism-oriented side effects. Reference: Bioorg Med Chem Lett. 2014 Feb 15;24(4):1071-4. https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(14)00027-4 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 34.0 | 106.79 |
The following data is based on the product molecular weight 318.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Mabuchi M, Shimizu T, Ueda M, Sasakawa Y, Nakao S, Ueda Y, Kawamura A, Tsujikawa K, Tanaka A. Improving the bioavailability and anticancer effect of the PCA-1/ALKBH3 inhibitor HUHS015 using sodium salt. In Vivo. 2015 Jan-Feb;29(1):39-43. PMID: 25600528. 2. Nakao S, Mabuchi M, Shimizu T, Itoh Y, Takeuchi Y, Ueda M, Mizuno H, Shigi N, Ohshio I, Jinguji K, Ueda Y, Yamamoto M, Furukawa T, Aoki S, Tsujikawa K, Tanaka A. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg Med Chem Lett. 2014 Feb 15;24(4):1071-4. doi: 10.1016/j.bmcl.2014.01.008. Epub 2014 Jan 11. PMID: 24461353. |
| In vivo protocol: | 1. Mabuchi M, Shimizu T, Ueda M, Sasakawa Y, Nakao S, Ueda Y, Kawamura A, Tsujikawa K, Tanaka A. Improving the bioavailability and anticancer effect of the PCA-1/ALKBH3 inhibitor HUHS015 using sodium salt. In Vivo. 2015 Jan-Feb;29(1):39-43. PMID: 25600528. 2. Nakao S, Mabuchi M, Shimizu T, Itoh Y, Takeuchi Y, Ueda M, Mizuno H, Shigi N, Ohshio I, Jinguji K, Ueda Y, Yamamoto M, Furukawa T, Aoki S, Tsujikawa K, Tanaka A. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg Med Chem Lett. 2014 Feb 15;24(4):1071-4. doi: 10.1016/j.bmcl.2014.01.008. Epub 2014 Jan 11. PMID: 24461353. |
1: Nakao S, Mabuchi M, Shimizu T, Itoh Y, Takeuchi Y, Ueda M, Mizuno H, Shigi N, Ohshio I, Jinguji K, Ueda Y, Yamamoto M, Furukawa T, Aoki S, Tsujikawa K, Tanaka A. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg Med Chem Lett. 24 (2014) 1071–1074.
