Taselisib (GDC0032)
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MedKoo CAT#: 205746

CAS#: 1282512-48-4

Description: Taselisib, also known as GDC0032 or RG7606, is a selective, potent, orally bioavailable inhibitor of PI3Ka with a Ki = 0.2nM, and with reduced inhibitory activity against PI3Kβ. This selectivity profile, and excellent pharmacokinetic and pharmaceutical properties, allowed for greater efficacy in vivo at the maximum tolerated dose relative to a pan Class I PI3K inhibitor in PIK3CA mutant xenografts. Notably, GDC-0032 preferentially inhibited PIK3CA mutant cells relative to cells with wild-type PI3K. GDC-0032 potently inhibits signal transduction downstream of PI3K and induces apoptosis at low concentrations in breast cancer cell lines and xenograft models that harbor PIK3CA mutations.


Chemical Structure

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Taselisib (GDC0032)
CAS# 1282512-48-4

Theoretical Analysis

MedKoo Cat#: 205746
Name: Taselisib (GDC0032)
CAS#: 1282512-48-4
Chemical Formula: C24H28N8O2
Exact Mass: 460.23
Molecular Weight: 460.530
Elemental Analysis: C, 62.59; H, 6.13; N, 24.33; O, 6.95

Price and Availability

Size Price Availability Quantity
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 800 Ready to ship
500mg USD 1650 Ready to ship
1g USD 2950 Ready to ship
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Synonym: GDC0032, GDC0032, GDC 0032, RG7604, RG7604, RG 7604, Taselisib

IUPAC/Chemical Name: 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide

InChi Key: BEUQXVWXFDOSAQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H28N8O2/c1-14(2)32-22(27-15(3)29-32)19-13-30-8-9-34-20-10-16(6-7-18(20)21(30)28-19)17-11-26-31(12-17)24(4,5)23(25)33/h6-7,10-14H,8-9H2,1-5H3,(H2,25,33)

SMILES Code: CC(C)(N1N=CC(C2=CC=C3C4=NC(C5=NC(C)=NN5C(C)C)=CN4CCOC3=C2)=C1)C(N)=O

Appearance: White to off-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: Taselisib (GDC-0032) is a potent PI3K inhibitor targets PIK3CA mutations, with Kis of 0.12 nM, 0.29 nM, 0.97 nM, and 9.1 nM for PI3Kδ, PI3Kα, PI3Kγ and PI3Kβ, respectively.
In vitro activity: Phosphorylated HER2 (pHER2), along with phosphorylated HER3 and phosphorylated EGFR, were induced following taselisib treatment in both the HER2+/PIK3CAWT AU565 and the HER2+/PIK3CAmut KPL-4 cells (Fig. 2C). Immunoblot analysis of a larger subset of HER2+ cell lines confirmed a consistent pattern of pHER2 upregulation following taselisib treatment in HER2+/PIK3CAmut cells, but this was not seen in HER2+/PIK3CAWT cells (Fig. 2D). PI3K pathway suppression and induction of apoptosis, as assessed by cleaved PARP and cleaved caspase 3, was induced by inhibition with the dual EGFR and HER2 inhibitor lapatinib in the HER2+/PIK3CAWT cell lines, whereas these effects were primarily induced by PI3K inhibition in the HER2+/PIK3CAmut cell lines (Fig. 2D; Supplementary Fig. S2B). Reference: Mol Cancer Ther. 2020 Jan;19(1):292-303. https://mct.aacrjournals.org/content/19/1/292.long
In vivo activity: Ten mice were randomized in two groups, control and taselisib. No signs of general toxicity were seen in any of the 2 treatment groups harboring the USC-xenograft and no animal died during the experiments or had to be prematurely sacrificed due to signs of systemic drug toxicity. One mouse in the control group had to be sacrificed after 7 days because it reached 1 cm3 in tumor volume while the remaining control animals had to be sacrificed within 2 weeks secondary to their tumor volume. Taselisib group showed a significant tumor growth inhibition after 14 days of treatment (P=0.007; Figure 5 panel A) and significantly improved OS when compared to the control group (P<0.0001; Figure 5 panel B). The mean survival of the taselisib-treated mice was 45 days. Reference: Gynecol Oncol. 2014 Nov; 135(2): 312–317. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270135/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 63.3 137.52
Ethanol 7.0 15.20

Preparing Stock Solutions

The following data is based on the product molecular weight 460.53 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.

Recalculate based on batch purity %
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. Moore HM, Savage HM, O'Brien C, Zhou W, Sokol ES, Goldberg ME, Metcalfe C, Friedman LS, Lackner MR, Wilson TR. Predictive and Pharmacodynamic Biomarkers of Response to the Phosphatidylinositol 3-Kinase Inhibitor Taselisib in Breast Cancer Preclinical Models. Mol Cancer Ther. 2020 Jan;19(1):292-303. doi: 10.1158/1535-7163.MCT-19-0284. Epub 2019 Sep 18. PMID: 31534012. 2. Lopez S, Schwab CL, Cocco E, Bellone S, Bonazzoli E, English DP, Schwartz PE, Rutherford T, Angioli R, Santin AD. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecol Oncol. 2014 Nov;135(2):312-7. doi: 10.1016/j.ygyno.2014.08.024. Epub 2014 Aug 27. PMID: 25172762; PMCID: PMC4270135. 3. Ndubaku CO, Heffron TP, Staben ST, Baumgardner M, Blaquiere N, Bradley E, Bull R, Do S, Dotson J, Dudley D, Edgar KA, Friedman LS, Goldsmith R, Heald RA, Kolesnikov A, Lee L, Lewis C, Nannini M, Nonomiya J, Pang J, Price S, Prior WW, Salphati L, Sideris S, Wallin JJ, Wang L, Wei B, Sampath D, Olivero AG. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem. 2013 Jun 13;56(11):4597-610. doi: 10.1021/jm4003632. Epub 2013 Jun 3. PMID: 23662903.
In vitro protocol: 1. Moore HM, Savage HM, O'Brien C, Zhou W, Sokol ES, Goldberg ME, Metcalfe C, Friedman LS, Lackner MR, Wilson TR. Predictive and Pharmacodynamic Biomarkers of Response to the Phosphatidylinositol 3-Kinase Inhibitor Taselisib in Breast Cancer Preclinical Models. Mol Cancer Ther. 2020 Jan;19(1):292-303. doi: 10.1158/1535-7163.MCT-19-0284. Epub 2019 Sep 18. PMID: 31534012. 2. Lopez S, Schwab CL, Cocco E, Bellone S, Bonazzoli E, English DP, Schwartz PE, Rutherford T, Angioli R, Santin AD. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecol Oncol. 2014 Nov;135(2):312-7. doi: 10.1016/j.ygyno.2014.08.024. Epub 2014 Aug 27. PMID: 25172762; PMCID: PMC4270135.
In vivo protocol: 1. Lopez S, Schwab CL, Cocco E, Bellone S, Bonazzoli E, English DP, Schwartz PE, Rutherford T, Angioli R, Santin AD. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecol Oncol. 2014 Nov;135(2):312-7. doi: 10.1016/j.ygyno.2014.08.024. Epub 2014 Aug 27. PMID: 25172762; PMCID: PMC4270135. 2. Ndubaku CO, Heffron TP, Staben ST, Baumgardner M, Blaquiere N, Bradley E, Bull R, Do S, Dotson J, Dudley D, Edgar KA, Friedman LS, Goldsmith R, Heald RA, Kolesnikov A, Lee L, Lewis C, Nannini M, Nonomiya J, Pang J, Price S, Prior WW, Salphati L, Sideris S, Wallin JJ, Wang L, Wei B, Sampath D, Olivero AG. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem. 2013 Jun 13;56(11):4597-610. doi: 10.1021/jm4003632. Epub 2013 Jun 3. PMID: 23662903.

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1: Lopez S, Schwab CL, Cocco E, Bellone S, Bonazzoli E, English DP, Schwartz PE,  Rutherford T, Angioli R, Santin AD. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecol Oncol. 2014 Aug 26. pii: S0090-8258(14)01277-3. doi: 10.1016/j.ygyno.2014.08.024. [Epub ahead of print] PubMed PMID: 25172762.