Deruxtecan
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MedKoo CAT#: 207106

CAS#: 1599440-13-7

Description: Deruxtecan, a topoisomerase I inhibitor, is an exatecan derivative (DX-8951 derivative) with a cleavable pepetide linker and a maleimide group. The maleimide group in Deruxtecan can react with antibody to form antibody-drug conguates (ADC) such as Trastuzumab deruxtecan (DS-8201a), which is a HER2-targeting antibody–drug conjugate. DS-8201a significantly suppressed tumor growth in an immunocompetent mouse model with human HER2-expressing CT26.WT (CT26.WThHER2) cells. DS-8201a is currently in clinical trials


Chemical Structure

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Deruxtecan
CAS# 1599440-13-7

Theoretical Analysis

MedKoo Cat#: 207106
Name: Deruxtecan
CAS#: 1599440-13-7
Chemical Formula: C52H56FN9O13
Exact Mass: 1033.3982
Molecular Weight: 1034.0684
Elemental Analysis: C, 60.40; H, 5.46; F, 1.84; N, 12.19; O, 20.11

Price and Availability

Size Price Availability Quantity
1.0mg USD 250.0 Ready to ship
5.0mg USD 750.0 Ready to ship
10.0mg USD 1350.0 Ready to ship
25.0mg USD 2950.0 Ready to ship
50.0mg USD 4720.0 Ready to ship
100.0mg USD 7552.0 Ready to ship
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Synonym: Deruxtecan, Trastuzumab deruxtecan; DS-8201a; DS8201a; DS 8201a; exatecan derivative; DX-8951 derivative; DX 8951; DX8951;

IUPAC/Chemical Name: Glycinamide, N-[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxohexyl]glycylglycyl-L-phenylalanyl-N-[[2-[[(1S,9S)-9-ethyl-5-fluoro-2,3,9,10,13,15-hexahydro-9-hydroxy-4-methyl-10,13-dioxo-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl]amino]-2-oxoethoxy]methyl]-

InChi Key: WXNSCLIZKHLNSG-MCZRLCSDSA-N

InChi Code: InChI=1S/C52H56FN9O13/c1-3-52(73)33-19-38-48-31(24-62(38)50(71)32(33)25-75-51(52)72)47-35(14-13-30-28(2)34(53)20-36(60-48)46(30)47)58-43(67)26-74-27-57-41(65)22-56-49(70)37(18-29-10-6-4-7-11-29)59-42(66)23-55-40(64)21-54-39(63)12-8-5-9-17-61-44(68)15-16-45(61)69/h4,6-7,10-11,15-16,19-20,35,37,73H,3,5,8-9,12-14,17-18,21-27H2,1-2H3,(H,54,63)(H,55,64)(H,56,70)(H,57,65)(H,58,67)(H,59,66)/t35-,37-,52-/m0/s1

SMILES Code: CC[C@@]1(O)C(OCC2=C1C=C3N(C2=O)CC(C3=NC4=CC(F)=C5C)=C6C4=C5CC[C@@H]6NC(COCNC(CNC([C@@H](NC(CNC(CNC(CCCCCN7C(C=CC7=O)=O)=O)=O)=O)CC8=CC=CC=C8)=O)=O)=O)=O

Appearance: 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

Shelf Life: >3 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: Deruxtecan is an ADC drug-linker conjugate composed of a derivative of DX-8951 (DXd) and a maleimide-GGFG peptide linker, used for synthesizing DS-8201 and U3-1402.
In vitro activity: The antitumor activity of [fam-] trastuzumab deruxtecan for CRC with five CRC cell lines that possess different biological characteristics was investigated. The expression of HER2 at both mRNA and protein levels in these various cell lines was first examined. Immunoblot analysis and RT and real-time polymerase chain reaction (PCR) analysis revealed that the amounts of HER2 protein and HER2 mRNA were much smaller in all the CRC cell lines than in NCI-N87 cells. [fam-] trastuzumab deruxtecan attenuated the viability of NCI-N87 cells, consistent with previous results, whereas all five CRC cell lines showed resistance to this agent. These findings suggested that the expression level of HER2 protein might determine sensitivity to [fam-] trastuzumab deruxtecan. Reference: Int J Cancer. 2019 Dec 15;145(12):3414-3424. https://pubmed.ncbi.nlm.nih.gov/31087550/
In vivo activity: The efficacy of [fam-] trastuzumab deruxtecan in HER2-expressing xenograft tumor models was tested. It was first confirmed that HER2 protein expression levels by immunohistochemistry (IHC) in subcutaneous tumors formed in nude mice by HCT116-Mock, HCT116-H2L or HCT116-H2H cells. Administration of [fam-] trastuzumab deruxtecan at a dose of 3.0 mg/kg markedly inhibited the growth of tumors formed by HCT116-H2L or HCT116-H2H cells but not that of those formed by HCT116-Mock cells. The extents of the inhibition by [fam-] trastuzumab deruxtecan were 60 and 93% compared to PBS vehicle for HCT116-H2L and HCT116-H2H cells, respectively, on day 24. Treatment with [fam-] trastuzumab deruxtecan had no effect on body weight in any of the three groups of mice. These findings thus indicated that the sensitivity of tumors to [fam-] trastuzumab deruxtecan in xenograft models is dependent on HER2 expression level and that such treatment is not associated with overt toxicity. Reference: Int J Cancer. 2019 Dec 15;145(12):3414-3424. https://pubmed.ncbi.nlm.nih.gov/31087550/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 67.5 65.28

Preparing Stock Solutions

The following data is based on the product molecular weight 1034.0684 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. Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-Targeting Antibody-Drug Conjugate, Trastuzumab Deruxtecan (DS-8201a), Enhances Antitumor Immunity in a Mouse Model. Mol Cancer Ther. 2018 Jul;17(7):1494-1503. doi: 10.1158/1535-7163.MCT-17-0749. Epub 2018 Apr 27. PMID: 29703841. 2. Takegawa N, Tsurutani J, Kawakami H, Yonesaka K, Kato R, Haratani K, Hayashi H, Takeda M, Nonagase Y, Maenishi O, Nakagawa K. [fam-] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification. Int J Cancer. 2019 Dec 15;145(12):3414-3424. doi: 10.1002/ijc.32408. Epub 2019 May 24. PMID: 31087550.
In vitro protocol: 1. Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-Targeting Antibody-Drug Conjugate, Trastuzumab Deruxtecan (DS-8201a), Enhances Antitumor Immunity in a Mouse Model. Mol Cancer Ther. 2018 Jul;17(7):1494-1503. doi: 10.1158/1535-7163.MCT-17-0749. Epub 2018 Apr 27. PMID: 29703841. 2. Takegawa N, Tsurutani J, Kawakami H, Yonesaka K, Kato R, Haratani K, Hayashi H, Takeda M, Nonagase Y, Maenishi O, Nakagawa K. [fam-] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification. Int J Cancer. 2019 Dec 15;145(12):3414-3424. doi: 10.1002/ijc.32408. Epub 2019 May 24. PMID: 31087550.
In vivo protocol: 1. Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-Targeting Antibody-Drug Conjugate, Trastuzumab Deruxtecan (DS-8201a), Enhances Antitumor Immunity in a Mouse Model. Mol Cancer Ther. 2018 Jul;17(7):1494-1503. doi: 10.1158/1535-7163.MCT-17-0749. Epub 2018 Apr 27. PMID: 29703841. 2. Takegawa N, Tsurutani J, Kawakami H, Yonesaka K, Kato R, Haratani K, Hayashi H, Takeda M, Nonagase Y, Maenishi O, Nakagawa K. [fam-] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification. Int J Cancer. 2019 Dec 15;145(12):3414-3424. doi: 10.1002/ijc.32408. Epub 2019 May 24. PMID: 31087550.

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1: Takegawa N, Tsurutani J, Kawakami H, Yonesaka K, Kato R, Haratani K, Hayashi H, Takeda M, Nonagase Y, Maenishi O, Nakagawa K. [fam-] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification. Int J Cancer. 2019 May 14. doi: 10.1002/ijc.32408. [Epub ahead of print] PubMed PMID: 31087550.

2: Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, Tsurutani J, Kadowaki S, Yamaguchi K, Iwasa S, Saito K, Fujisaki Y, Sugihara M, Shahidi J, Doi T. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):827-836. doi: 10.1016/S1470-2045(19)30088-9. Epub 2019 Apr 29. Erratum in: Lancet Oncol. 2019 May 10;:. PubMed PMID: 31047804.

3: Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29. Erratum in: Lancet Oncol. 2019 May 10;:. PubMed PMID: 31047803.

4: Rinnerthaler G, Gampenrieder SP, Greil R. HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer. Int J Mol Sci. 2019 Mar 5;20(5). pii: E1115. doi: 10.3390/ijms20051115. Review. PubMed PMID: 30841523; PubMed Central PMCID: PMC6429068.

5: Nakada T, Sugihara K, Jikoh T, Abe Y, Agatsuma T. The Latest Research and Development into the Antibody-Drug Conjugate, [fam-] Trastuzumab Deruxtecan (DS-8201a), for HER2 Cancer Therapy. Chem Pharm Bull (Tokyo). 2019;67(3):173-185. doi: 10.1248/cpb.c18-00744. Review. PubMed PMID: 30827997.

6: Bartsch R, Bergen E. ASCO 2018: highlights in HER2-positive metastatic breast cancer. Memo. 2018;11(4):280-283. doi: 10.1007/s12254-018-0441-x. Epub 2018 Oct 11. Review. PubMed PMID: 30595754; PubMed Central PMCID: PMC6280772.

7: Nagai Y, Oitate M, Shiozawa H, Ando O. Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys. Xenobiotica. 2019 Sep;49(9):1086-1096. doi: 10.1080/00498254.2018.1531158. Epub 2019 Jan 4. PubMed PMID: 30351177.

8: Lote H, Valeri N, Chau I. HER2 inhibition in gastro-oesophageal cancer: A review drawing on lessons learned from breast cancer. World J Gastrointest Oncol. 2018 Jul 15;10(7):159-171. doi: 10.4251/wjgo.v10.i7.159. Review. PubMed PMID: 30079142; PubMed Central PMCID: PMC6068859.

9: Trastuzumab Deruxtecan Targets HER2+ Cancers. Cancer Discov. 2018 Aug;8(8):OF5. doi: 10.1158/2159-8290.CD-NB2018-083. Epub 2018 Jun 27. PubMed PMID: 29950345.

10: Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-Targeting Antibody-Drug Conjugate, Trastuzumab Deruxtecan (DS-8201a), Enhances Antitumor Immunity in a Mouse Model. Mol Cancer Ther. 2018 Jul;17(7):1494-1503. doi: 10.1158/1535-7163.MCT-17-0749. Epub 2018 Apr 27. PubMed PMID: 29703841.

11: Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, Shimizu C, Shimoi T, Kuboki Y, Matsubara N, Kitano A, Jikoh T, Lee C, Fujisaki Y, Ogitani Y, Yver A, Tamura K. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017 Nov;18(11):1512-1522. doi: 10.1016/S1470-2045(17)30604-6. Epub 2017 Oct 13. PubMed PMID: 29037983.