TAK-285
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MedKoo CAT#: 202721

CAS#: 871026-44-7

Description: TAK-285 is a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2. Methods: TAK-285 is currently being developed by Takeda. TAK-285 was found to be well tolerate in Phase I trials. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300 mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300 mg b.i.d. The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.


Chemical Structure

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TAK-285
CAS# 871026-44-7

Theoretical Analysis

MedKoo Cat#: 202721
Name: TAK-285
CAS#: 871026-44-7
Chemical Formula: C26H25ClF3N5O3
Exact Mass: 547.1598
Molecular Weight: 547.96
Elemental Analysis: C, 56.99; H, 4.60; Cl, 6.47; F, 10.40; N, 12.78; O, 8.76

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 650.0 Ready to ship
200.0mg USD 1050.0 Ready to ship
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Synonym: TAK285, TAK285, TAK 285

IUPAC/Chemical Name: N-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl)-3-hydroxy-3-methylbutanamide

InChi Key: ZYQXEVJIFYIBHZ-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H25ClF3N5O3/c1-25(2,37)14-22(36)31-9-11-35-10-8-20-23(35)24(33-15-32-20)34-17-6-7-21(19(27)13-17)38-18-5-3-4-16(12-18)26(28,29)30/h3-8,10,12-13,15,37H,9,11,14H2,1-2H3,(H,31,36)(H,32,33,34)

SMILES Code: CC(C)(O)CC(NCCN1C=CC2=NC=NC(NC3=CC=C(OC4=CC=CC(C(F)(F)F)=C4)C(Cl)=C3)=C21)=O

Appearance: White to off-white solid powder

Purity: >93 % (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: >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

Biological target: TAK-285 is a HER2 and EGFR(HER1) inhibitor with IC50 of 17 nM and 23 nM, respectively.
In vitro activity: TAK-285 had a growth inhibitory effect in multiple cell lines. Sensitivities of various cell lines to growth inhibition by TAK-285 are shown in Table 1. In general, cells with higher expression of HER2 were more sensitive to TAK-285, but A-431 cells, which overexpress EGFR, were also sensitive to TAK-285. The IC50 for BT-474 cells was 0.017 µmol/L compared with 1.1 and 20 µmol/L in A-431 and MRC-5 cells which do not overexpress HER2. In other experiments, TAK-285 inhibited HER2 phosphorylation in BT-474 cells with IC50 values of 0.0093 µmol/L (95% CI 0.0065, 0.012). TAK-285 also inhibited Akt and MAPK phosphorylation in a dose-dependent manner, with IC50 values of 0.015 µmol/L (95% CI: 0.011, 0.018) and <0.0063 µmol/L, respectively. In A-431 cells, the IC50 value for TAK-285 inhibition of EGFR phosphorylation was 0.053 µmol/L (95% CI 0.040, 0.069). Reference: 2013 Aug 16;4(7):557-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753530/
In vivo activity: The tumor growth inhibitory effect of TAK-285 was tested in a murine intracranial injection model of brain metastases using BT-474-derived cerebral xenografts that resulted in highly reproducible tumor growth in a defined intracranial region (Figure 5A). For these experiments, a line of luciferase-detectable BT-474 cells (BTLUC) that allowed non-invasive monitoring of intracranial xenograft growth (Figure 5B) was developed. BTLUC cells possessed highly activated HER2 with phosphorylation comparable to parental BT-474 cells (Figure 5C) and sensitivity to TAK-285 with IC50 value of 90 nmol/L (95% CI: 76-107nmol/L). TAK-285 inhibited intracranial xenograft growth with T/C values of 44% on day 41 (Figure 6, P = 0.011 vs control). Reference: 2013 Aug 16;4(7):557-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753530/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 80.0 146.0
Ethanol 54.0 98.55

Preparing Stock Solutions

The following data is based on the product molecular weight 547.96 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. Nakayama A, Takagi S, Yusa T, Yaguchi M, Hayashi A, Tamura T, Kawakita Y, Ishikawa T, Ohta Y. Antitumor Activity of TAK-285, an Investigational, Non-Pgp Substrate HER2/EGFR Kinase Inhibitor, in Cultured Tumor Cells, Mouse and Rat Xenograft Tumors, and in an HER2-Positive Brain Metastasis Model. J Cancer. 2013 Aug 16;4(7):557-65. doi: 10.7150/jca.6689. PMID: 23983820; PMCID: PMC3753530.
In vitro protocol: 1. Nakayama A, Takagi S, Yusa T, Yaguchi M, Hayashi A, Tamura T, Kawakita Y, Ishikawa T, Ohta Y. Antitumor Activity of TAK-285, an Investigational, Non-Pgp Substrate HER2/EGFR Kinase Inhibitor, in Cultured Tumor Cells, Mouse and Rat Xenograft Tumors, and in an HER2-Positive Brain Metastasis Model. J Cancer. 2013 Aug 16;4(7):557-65. doi: 10.7150/jca.6689. PMID: 23983820; PMCID: PMC3753530.
In vivo protocol: 1. Nakayama A, Takagi S, Yusa T, Yaguchi M, Hayashi A, Tamura T, Kawakita Y, Ishikawa T, Ohta Y. Antitumor Activity of TAK-285, an Investigational, Non-Pgp Substrate HER2/EGFR Kinase Inhibitor, in Cultured Tumor Cells, Mouse and Rat Xenograft Tumors, and in an HER2-Positive Brain Metastasis Model. J Cancer. 2013 Aug 16;4(7):557-65. doi: 10.7150/jca.6689. PMID: 23983820; PMCID: PMC3753530.

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1: Ishikawa T, Seto M, Banno H, Kawakita Y, Oorui M, Taniguchi T, Ohta Y, Tamura T,  Nakayama A, Miki H, Kamiguchi H, Tanaka T, Habuka N, Sogabe S, Yano J, Aertgeerts K, Kamiyama K. Design and Synthesis of Novel Human Epidermal Growth Factor Receptor 2 (HER2)/Epidermal Growth Factor Receptor (EGFR) Dual Inhibitors  Bearing a Pyrrolo[3,2-d]pyrimidine Scaffold. J Med Chem. 2011 Nov 4. [Epub ahead  of print] PubMed PMID: 22003817.

TAK-285

10.0mg / USD 150.0