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Purity: ≥98%
3α-Aminocholestane (also known as 3AC) is a potent and selective SH2 domain-containing inositol-5′-phosphatase 1 (SHIP1) inhibitor with immunomodulatory and antitumor effects. It inhibits SHIP1 with an IC50 of ~2.5 μM. 3AC shows no inhibition on SHIP2 or PTEN. Many tumors present with increased activation of the phosphatidylinositol 3-kinase (PI3K)-PtdIns(3,4,5)P(3)-protein kinase B (PKB/Akt) signaling pathway. It has long been thought that the lipid phosphatases SH2 domain-containing inositol-5'-phosphatase 1 (SHIP1) and SHIP2 act as tumor suppressors by counteracting with the survival signal induced by this pathway through hydrolysis or PtdIns(3,4,5)P(3) to PtdIns(3,4)P(2). However, a growing body of evidence suggests that PtdInd(3,4)P(2) is capable of, and essential for, Akt activation, thus suggesting a potential role for SHIP1/2 enzymes as proto-oncogenes. 3AC is capable of killing malignant hematologic cells. In vivo growth of MM cells is blocked by treatment of mice with the SHIP1 inhibitor 3AC.
| ln Vitro |
3α-Aminocholestane (3AC) therapy substantially reduces OPM2 cell viability. When compared to OPM2 cells, RPMI8226 and U266 cells exhibit much lower sensitivity to 3α-Aminocholestane treatment; yet, viability is significantly reduced at doses of ≥12.5 μM. After being treated for 36 hours with 3α-Aminocholestane, the proportion of cells in the S phase is significantly decreased, and the number of cells in the G2/M phase increases. On the other hand, in the less proliferative RPMI8226 and U266 cells, treatment with 3α-Aminocholestane blocks cell cycle progression in the G0 /G1 phase and results in a lower percentage of cells progressing through the S phase[2].
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| ln Vivo |
Upon OPM2 challenge, it is discovered that 3α-Aminocholestane (3AC) leads to decreased multiple myeloma (MM) growth in vivo, as measured by the amount of free human Igλ light chain in the plasma. Furthermore, peripheral blood from mice treated with 3-aminocholestane shows less circulating OPM2 cells, as detected by human HLA-ABC labeling, as compared to vehicle controls. Most notably, mice treated with 3α-Aminocholestane had much improved survival rates following tumor challenge. When mice treated with 3α-Aminocholestane fail to respond to treatment, it is discovered that MM tumors have an overexpression of SHIP2, which is similar to when OPM2 cells are treated in vitro and implies that tumor cells with higher SHIP2 expression may be chosen by SHIP1 inhibition[2].
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| References |
[1]. Chen Z, et al. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature. 2015 May 21;521(7552):357-61.
[2]. Gwenny M Fuhler, et al. Therapeutic Potential of SH2 Domain-Containing Inositol-5′-Phosphatase 1 (SHIP1) and SHIP2 Inhibition in Cancer. Mol Med. 2012 Feb 10;18:65-75 |
| Molecular Formula |
C27H49N
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| Molecular Weight |
387.69
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| CAS # |
2206-20-4
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| SMILES |
CC(C)CCC[C@@H](C)[C@H]1CC[C@@]2([H])[C@]3([H])CCC4C[C@H](N)CC[C@]4(C)[C@@]3([H])CC[C@]12C
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| Chemical Name |
(3R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-amine
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| Synonyms |
3α-Aminocholestane; 3AC, 3-AC, 3 AC
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (8.38 mM) (saturation unknown) in 10% EtOH + 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 32.5 mg/mL clear EtOH 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: ≥ 3.25 mg/mL (8.38 mM) (saturation unknown) in 10% EtOH + 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 32.5 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5794 mL | 12.8969 mL | 25.7938 mL | |
| 5 mM | 0.5159 mL | 2.5794 mL | 5.1588 mL | |
| 10 mM | 0.2579 mL | 1.2897 mL | 2.5794 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.
Small molecule inhibition of Inpp5d induces hyperactivation of Syk and triggers a deletional checkpoint in pre-B ALL cells.Nature.2015May 21;521(7552):357-61. |
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SHIP1 inhibition reduces viable cell numbers and either G2/M or G0/G1 cell cycle arrest.Mol Med.2012 Feb 10;18:65-75. |
SHIP1 inhibition affects apoptosis induction differently in MM cell lines.Mol Med.2012 Feb 10;18:65-75. |
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