Name: DOXO-EMCH
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

1H-Pyrrole-1-hexanoic acid, 2,5-dihydro-2,5-dioxo-, [1-[(2S,4S)-4-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-2-naphthacenyl]-2-hydroxyethylidene]hydrazide; 1H-Pyrrole-1-hexanoic acid, 2,5-dihydro-2,5-dioxo-, [1-[4-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-2-naphthacenyl]-2-hydroxyethylidene]hydrazide, (2S-cis)-; Doxorubicin-EMCH

IUPAC Name

N-[[1-[(2S,4S)-4-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-hydroxyethylidene]amino]-6-(2,5-dioxopyrrol-1-yl)hexanamide

Canonical SMILES

CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=NNC(=O)CCCCCN6C(=O)C=CC6=O)CO)O)N)O

InChI

InChI=1S/C37H42N4O13/c1-17-32(46)20(38)13-27(53-17)54-22-15-37(51,23(16-42)39-40-24(43)9-4-3-5-12-41-25(44)10-11-26(41)45)14-19-29(22)36(50)31-30(34(19)48)33(47)18-7-6-8-21(52-2)28(18)35(31)49/h6-8,10-11,17,20,22,27,32,42,46,48,50-51H,3-5,9,12-16,38H2,1-2H3,(H,40,43)/t17-,20-,22-,27-,32+,37-/m0/s1

InChIKey

OBMJQRLIQQTJLR-FRTGXRTISA-N

Density

1.60±0.1 g/cm3

Solubility

Soluble in DMSO

PSA

267.84000

Appearance

Red solid powder

Shelf Life

≥360 days if stored properly

Shipping

Room temperature, or blue ice upon request.

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

Current Developer

Innovive Pharmaceuticals and CytRx Corporation

In Vitro

The LD50 of DOXO-EMCH was >60 mg/kg doxorubicin equivalents in both male and female mice (the LD50 of doxorubicin in CD-1 mice is -12 mg/kg). In Sprague-Dawley rats, the LD50 was 23.4 and 45.9 mg/kg doxorubicin equivalents for males and females, respectively.

In Vivo

In Beagle dogs, LD10 was not reached for DOXO-EMCH at 4.5 mg/kg doxorubicin equivalents. A four-cycle intravenous study with DOXO-EMCH at dose levels of 4 x 2.5, 5.0 or 7.5 mg/kg doxorubicin equivalents in rats revealed approximately three-fold less side effects on the hemolymphoreticular system when compared to 4 x 2.5 mg/kg doxorubicin dose, whereas effects on the testes/oligospermia seem to be comparable between both drugs at equitoxic dose. The toxicity studies with DOXO-EMCH in mice, rats or dogs have not identified any other special toxicity when compared to the toxicity data for doxorubicin. Preclinical tolerance of DOXO-EMCH was higher in mice, rats and dogs compared to doxorubicin. A dose of 20 mg/m2 doxorubicin equivalents was recommended as the starting dose for a phase I study with DOXO-EMCH.

NCT Number	Condition Or Disease	Phase	Start Date	Sponsor	Status
NCT02029430	Kaposi's Sarcoma	Phase 2	2016-10-19	CytRx	Completed
NCT01337505	Malignant Solid Tumour	Phase 1	2013-02-13	CytRx	Completed
NCT02235688	Metastatic Solid Tumors	Phase 1	2017-06-07	CytRx	Completed
NCT02014844	Glioblastoma	Phase 2	2017-01-06	CytRx	Completed
NCT01673438	Advanced Solid Tumor	Phase 1	2014-04-21	CytRx	Completed

DOXO-EMCH is a defined ADC Cytotoxin with Linker, consisting of the anthracycline payload doxorubicin (DOXO) attached via a maleimide-containing EMCH linker. This design ensures that the ADC payload remains stable in circulation and is released specifically inside antigen-positive tumor cells. As a potent ADC Cytotoxin, DOXO-EMCH delivers doxorubicin efficiently, enabling DNA intercalation and topoisomerase II inhibition, which induces apoptosis through controlled intracellular release.

The mechanism of DOXO-EMCH involves antibody-mediated binding to target antigens and internalization into tumor cells. Once inside lysosomes, the EMCH linker undergoes cleavage, releasing the doxorubicin payload directly within the cell. This selective release ensures that the ADC payload exerts its DNA-intercalating and cytotoxic activity specifically in tumor cells, achieving potent anticancer effects while minimizing systemic exposure. The maleimide functional group provides stable conjugation to antibodies.

DOXO-EMCH allows stable conjugation to monoclonal antibodies, producing homogeneous ADC Cytotoxins with Linker. The cleavable EMCH linker ensures reliable intracellular payload release and reproducible cytotoxic performance. Its chemical properties, including solubility, linker stability, and controlled cleavage, enable consistent ADC assembly and precise delivery of doxorubicin in antigen-positive cells.

Applications of DOXO-EMCH focus on its function as a defined ADC payload-linker combination for constructing homogeneous antibody-drug conjugates. The cleavable EMCH linker provides controlled intracellular release of doxorubicin, producing consistent DNA intercalation and cytotoxic effects. This reagent delivers potent, targeted activity in ADC Cytotoxins with Linker, supporting precise intracellular payload delivery in oncology-focused ADC development and research.

1.A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma.

Chawla SP1, Chua VS, Hendifar AF, Quon DV, Soman N, Sankhala KK, Wieland DS, Levitt DJ. Cancer. 2015 Feb 15;121(4):570-9. doi: 10.1002/cncr.29081. Epub 2014 Oct 13.

BACKGROUND: Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD).

2.Therapeutic efficacy of aldoxorubicin in an intracranial xenograft mouse model of human glioblastoma.

Marrero L1, Wyczechowska D2, Musto AE3, Wilk A2, Vashistha H2, Zapata A2, Walker C2, Velasco-Gonzalez C4, Parsons C2, Wieland S5, Levitt D5, Reiss K2, Prakash O2. Neoplasia. 2014 Oct 23;16(10):874-82. doi: 10.1016/j.neo.2014.08.015. eCollection 2014.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents-3/4 maximum tolerated dose (MTD)], Doxo [6 mg/kg (3/4 MTD)], or vehicle.

3.First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial.

Chawla SP1, Papai Z2, Mukhametshina G3, Sankhala K4, Vasylyev L5, Fedenko A6, Khamly K7, Ganjoo K8, Nagarkar R9, Wieland S10, Levitt DJ10. JAMA Oncol. 2015 Dec;1(9):1272-80. doi: 10.1001/jamaoncol.2015.3101.

IMPORTANCE: Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies.

What is DOXO-EMCH?

DOXO-EMCH is a doxorubicin-based ADC linker-payload conjugate designed for targeted chemotherapy. It utilizes a maleimide-functionalized EMCH linker for conjugation to antibodies, enabling selective intracellular release of doxorubicin in tumor cells while reducing systemic toxicity.

12/5/2019

We are interested in how DOXO-EMCH releases doxorubicin.

The EMCH linker in DOXO-EMCH is cleaved under intracellular reducing conditions after ADC internalization, releasing doxorubicin directly inside target cells. This mechanism enhances cytotoxicity specifically in cancer cells while maintaining plasma stability.

15/9/2020

Could you advise what ADC research applications involve DOXO-EMCH?

DOXO-EMCH is widely used in oncology ADC research, supporting preclinical and early clinical studies. Its cleavable linker allows assessment of drug release kinetics, intracellular activity, and therapeutic efficacy in various tumor models.

20/6/2022

Could you kindly explain what stability characteristics DOXO-EMCH offers?

DOXO-EMCH exhibits high plasma stability due to the EMCH linker, reducing premature doxorubicin release. This stability ensures predictable ADC performance, consistent dosing, and reliable experimental evaluation.

21/12/2020

Dear BOC Sciences, can DOXO-EMCH be conjugated to different antibodies?

Yes, DOXO-EMCH can be conjugated to cysteine residues of various monoclonal antibodies, enabling flexible ADC design. Researchers can optimize drug-antibody ratios and target specificity for preclinical and clinical studies.

13/2/2022

— Dr. James Parker, Senior Scientist (USA)

DOXO-EMCH purity and stability were excellent for precise ADC conjugation.

20/6/2022

— Dr. Olivia Harris, ADC Chemist (UK)

Batch uniformity ensured reproducible cytotoxicity assays across experiments.

13/2/2022

— Dr. Claire Dupont, ADC Development Manager (France)

For DOXO-EMCH, BOC Sciences demonstrated exceptional expertise. The compound arrived with outstanding documentation, and its performance in conjugation studies confirmed their reputation as a dependable supplier.

21/12/2020

— Dr. Anya Sokolova, Principal Investigator (Czech Republic)

We were in a rush to complete our proof-of-concept study and needed a reliable supply of DOXO-EMCH. BOC Sciences provided a high-quality product on a very tight timeline. Their professional service and rapid delivery were instrumental in us hitting our project milestones. A great partner for our preclinical needs.

12/5/2019

— Dr. Lena Ivanova, Principal Investigator (Czech Republic)

Needed a fast turnaround on a quality product. BOC Sciences delivered DOXO-EMCH quickly, which was essential for us to hit our project milestones. Great service.

— Mr. Stefan Kraus, Senior Chemist (Germany)

DOXO-EMCH provided by BOC Sciences was instrumental in advancing our conjugation research. Its stability and reproducibility ensured smooth experimental progression, saving our team significant time.

15/9/2020