Synonym
INK1117; INK-1117; INK 1117; MLN1117; MLN 1117; MLN-1117; TAK-117; TAK 117; TAK117; Serabelisib
IUPAC/Chemical Name
[6-(2-amino-5-benzoxazolyl)imidazo[1,2-a]pyridin-3-yl]-4-morpholinyl-methanone
InChi Key
BLGWHBSBBJNKJO-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H17N5O3/c20-19-22-14-9-12(1-3-16(14)27-19)13-2-4-17-21-10-15(24(17)11-13)18(25)23-5-7-26-8-6-23/h1-4,9-11H,5-8H2,(H2,20,22)
SMILES Code
O=C(C1=CN=C2C=CC(C3=CC=C(OC(N)=N4)C4=C3)=CN21)N5CCOCC5
Appearance
Brown solid powder
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
>5 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
INK1117 has demonstrated significant efficacy in several PI3Kα mutant-specific preclinical mouse xenograft tumor models. Moreover, daily oral administration of INK1117 inhibited tumor growth in a dose-dependent manner with a predicted PK/PD relationship, was well tolerated at a range of efficacious doses, and exhibited several differentiating features from less selective inhibitors that target the PI3K/Akt/mTOR pathway. A Phase I dose escalation study is underway to evaluate the safety, tolerability and pharmacokinetics of single-agent INK1117 in patients with advanced solid malignancies who have tumors characterized by the presence of a PIK3CA mutation. (source: http://www.intellikine.com/pipeline/pi3kalpha_inhibitors.html).
Biological target:
Serabelisib (MLN1117) is a selective p110α inhibitor with an IC50 of 15 nM.
In vitro activity:
The effects of inhibitors on the proliferation of purified, CFSE-labeled B cells were compared. Statistical analysis of normalized data showed that the effects of GDC-0941 and IC87114 were highly significant, yet there was no significant effect of 1 μm A66, MLN1117, or TGX-221. At a higher concentration (2 μm), A66 or MLN1117 did significantly suppress B cell proliferation driven by anti-IgM alone but not by anti-IgM plus IL-4 (Fig. 4, A and B). Notably, CFSE histograms for three independent experiments did show a consistent, dose-dependent reduction in the extent of B cell division by each of the isoform-selective PI3K inhibitors (data not shown). Similar results were obtained using human peripheral blood B cells stimulated with anti-human IgD and IL-4 (Fig. 4C). Next the effects of PI3K inhibitors were tested on survival of purified B cells cultured in the presence of the cytokines BAFF or IL-4. At higher concentrations (1 μm) both A66 and MLN1117 caused only a minor decrease in survival.
Reference: J Biol Chem. 2013 Feb 22; 288(8): 5718–5731. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581375/
In vivo activity:
To compare the effects of PI3K inhibitors on B cell and T cell-mediated immune responses in vivo, antibody production was measured in mice vaccinated with hapten-carrier conjugates. To model T cell-independent antibody responses driven by BCR crosslinking, TNP-Ficoll was used as the immunogen. GDC-0941 treatment abrogated TNP-specific IgG3 production (Fig. 9A). This indicates that the T cell-independent IgG3 response is completely PI3K dependent. Treatment with MLN1117 at 30 and 60 mg/kg caused little reduction of TNP-specific IgG3 (Fig. 9A). Notably, reduction of TNP-specific IgG3 was observed at higher doses of MLN1117 (120 mg/kg), consistent with the partial reduction in cell division in B cells treated with MLN1117 before anti-IgM stimulation in vitro. However, 120 mg/kg is above the effective dose of MLN1117 for tumor growth inhibition (30–60 mg/kg).
Reference: J Biol Chem. 2013 Feb 22; 288(8): 5718–5731. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581375/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
4.0 |
11.01 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
363.38
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:
1. So L, Yea SS, Oak JS, Lu M, Manmadhan A, Ke QH, Janes MR, Kessler LV, Kucharski JM, Li LS, Martin MB, Ren P, Jessen KA, Liu Y, Rommel C, Fruman DA. Selective inhibition of phosphoinositide 3-kinase p110α preserves lymphocyte function. J Biol Chem. 2013 Feb 22;288(8):5718-31. doi: 10.1074/jbc.M112.379446. Epub 2012 Dec 28. PMID: 23275335; PMCID: PMC3581375. 2. Yea SS, So L, Mallya S, Lee J, Rajasekaran K, Malarkannan S, Fruman DA. Effects of novel isoform-selective phosphoinositide 3kinase inhibitors on natural killer cell function. PLoS One. 2014 Jun 10;9(6):e99486. doi: 10.1371/journal.pone.0099486. PMID: 24915189; PMCID: PMC4051752.
In vitro protocol:
1. So L, Yea SS, Oak JS, Lu M, Manmadhan A, Ke QH, Janes MR, Kessler LV, Kucharski JM, Li LS, Martin MB, Ren P, Jessen KA, Liu Y, Rommel C, Fruman DA. Selective inhibition of phosphoinositide 3-kinase p110α preserves lymphocyte function. J Biol Chem. 2013 Feb 22;288(8):5718-31. doi: 10.1074/jbc.M112.379446. Epub 2012 Dec 28. PMID: 23275335; PMCID: PMC3581375. 2. Yea SS, So L, Mallya S, Lee J, Rajasekaran K, Malarkannan S, Fruman DA. Effects of novel isoform-selective phosphoinositide 3kinase inhibitors on natural killer cell function. PLoS One. 2014 Jun 10;9(6):e99486. doi: 10.1371/journal.pone.0099486. PMID: 24915189; PMCID: PMC4051752.
In vivo protocol:
1. So L, Yea SS, Oak JS, Lu M, Manmadhan A, Ke QH, Janes MR, Kessler LV, Kucharski JM, Li LS, Martin MB, Ren P, Jessen KA, Liu Y, Rommel C, Fruman DA. Selective inhibition of phosphoinositide 3-kinase p110α preserves lymphocyte function. J Biol Chem. 2013 Feb 22;288(8):5718-31. doi: 10.1074/jbc.M112.379446. Epub 2012 Dec 28. PMID: 23275335; PMCID: PMC3581375. 2. Yea SS, So L, Mallya S, Lee J, Rajasekaran K, Malarkannan S, Fruman DA. Effects of novel isoform-selective phosphoinositide 3kinase inhibitors on natural killer cell function. PLoS One. 2014 Jun 10;9(6):e99486. doi: 10.1371/journal.pone.0099486. PMID: 24915189; PMCID: PMC4051752.
1: Yea SS, So L, Mallya S, Lee J, Rajasekaran K, Malarkannan S, Fruman DA. Effects of novel isoform-selective phosphoinositide 3-kinase inhibitors on natural killer cell function. PLoS One. 2014 Jun 10;9(6):e99486. doi: 10.1371/journal.pone.0099486. eCollection 2014. PubMed PMID: 24915189; PubMed Central PMCID: PMC4051752.
2: So L, Yea SS, Oak JS, Lu M, Manmadhan A, Ke QH, Janes MR, Kessler LV, Kucharski JM, Li LS, Martin MB, Ren P, Jessen KA, Liu Y, Rommel C, Fruman DA. Selective inhibition of phosphoinositide 3-kinase p110α preserves lymphocyte function. J Biol Chem. 2013 Feb 22;288(8):5718-31. doi: 10.1074/jbc.M112.379446. Epub 2012 Dec 28. PubMed PMID: 23275335; PubMed Central PMCID: PMC3581375.
