Name: Duocarmycin B1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

Antibiotic DC 89B1; 1H-Pyrrolo3,2-fquinoline-2-carboxylic acid, 8-bromo-2,3,6,7,8,9-hexahydro-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl-, methyl ester, (2R,8S)-; Duocarmycin B(sub 1)

IUPAC Name

methyl (2R,8S)-8-bromo-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,7,8,9-tetrahydropyrrolo[3,2-f]quinoline-2-carboxylate

Canonical SMILES

N1(C[C@H](Cc2c3c(c(cc12)O)N[C@](C3=O)(C(=O)OC)C)Br)C(=O)c1[nH]c2c(c1)cc(c(c2OC)OC)OC

InChI

InChI=1S/C26H26BrN3O8/c1-26(25(34)38-5)23(32)18-13-8-12(27)10-30(15(13)9-16(31)20(18)29-26)24(33)14-6-11-7-17(35-2)21(36-3)22(37-4)19(11)28-14/h6-7,9,12,28-29,31H,8,10H2,1-5H3/t12-,26+/m0/s1

InChIKey

SUWUAMDOMCWKCL-GWQKEKGPSA-N

Solubility

Soluble in ethanol, methanol, chloroform, DMSO

Appearance

Yellow Powder

Shipping

Room temperature

In Vitro

Duocarmycin B1, B2, C1 and C2, from which the cyclopropane ring structure is absent. Duocarmycins were potent cytotoxic compounds to cells. The cytotoxic activity seen on Balb 3T3/H-ras cells after 72 h drug exposure was in the following order (IC50 (nM): concentration for 50% growth inhibition); SA (0.05) > A (0.3) > B2 (1.5) > B1 (3.0) > C2 (20) > C1 (40). Average minimum inhibitory concentrations (MICs) of duocarmycins against microorganisms showed essentially the same ranking order as that of cytotoxicity. There was a large difference between SA and A in their stability in aqueous solvents. For halogenated seco-compounds, a good correlation was found between their cytotoxicities in vitro and their conversion rate to duocarmycin A, suggesting that halogenated seco-compounds undergo closure to the spirocyclopropylhexadienone structure, the pertinent active form, in cells.

Duocarmycin B1 is a highly potent DNA minor-groove alkylating agent and a prominent ADC cytotoxin widely used as an ADC payload in antibody-drug conjugates. Its mechanism involves selective binding to the minor groove of DNA, resulting in irreversible alkylation and DNA strand cleavage. This action triggers apoptosis in rapidly dividing tumor cells, making Duocarmycin B1 an ideal payload for targeted oncology therapies requiring extreme cytotoxic potency.

Within antibody-drug conjugates, Duocarmycin B1 is conjugated to monoclonal antibodies via cleavable or non-cleavable linker systems to enable selective payload release inside tumor cells. The ADC remains stable in circulation, preventing premature release and off-target toxicity, while enzymatic cleavage or chemical activation inside the tumor microenvironment releases the active cytotoxin. This targeted delivery ensures potent antitumor activity at low drug-to-antibody ratios (DARs) and enhances the therapeutic index of ADC constructs.

Applications of Duocarmycin B1 include its integration into experimental ADCs targeting both hematologic malignancies and solid tumors, such as breast, lung, ovarian cancers, and lymphomas. Its chemical versatility supports conjugation with various linker chemistries, improving stability, intracellular release, and pharmacokinetic profiles.

1. Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group

A Okamoto, S Nagamura, M Okabe, N Amishiro, E Kobayashi, H Saito, K Gomi Bioorg Med Chem . 2000 Jul;8(7):1637-43. doi: 10.1016/s0968-0896(00)00086-9.

A series of A-ring pyrrole derivatives of duocarmycin bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. New Seg-B analogues bearing beta-(5',6',7'-trimethoxy-2'-indolyl)acryloyl group containing double bond as spacer had lower peripheral blood toxicity than the derivatives bearing 5',6',7'-trimethoxyindole-2'-carboxyl group in Seg-B of the natural type. Moreover, most of them exhibited potent antitumor activity against in vivo murine tumor models.

2. Synthesis and antitumor activity of water-soluble duocarmycin B1 prodrugs

A Asai, S Nagamura, E Kobayashi, H Saito, K Gomi Bioorg Med Chem Lett . 1999 Oct 18;9(20):2995-8. doi: 10.1016/s0960-894x(99)00518-1.

The water-soluble duocarmycin B1 prodrugs such as glycoside 3, phosphate 4 and carbamate 5 were synthesized for improving biological and pharmaceutical profiles of duocarmycin. Among these prodrugs, N-methylpiperazinylcarbamoyl derivative 5 exhibited potent antitumor activity against several human tumors in vivo.

3. Interconversion and stability of duocarmycins, a new family of antitumor antibiotics: correlation to their cytotoxic and antimicrobial activities in vitro

A Mihara, H Nakano, T Ogawa, I Takahashi, K Takahashi, M Ichimura Oncol Res . 1993;5(4-5):165-71.

Stability and interconversion of duocarmycins were studied in relation to their cytotoxicities and antimicrobial activities. The compounds studied included duocarmycin A and SA, which have a spirocyclopropylhexadienone moiety, and four halogenated seco-compounds of duocarmycin A: duocarmycin B1, B2, C1 and C2, from which the cyclopropane ring structure is absent. Duocarmycins were potent cytotoxic compounds to cells. The cytotoxic activity seen on Balb 3T3/H-ras cells after 72 h drug exposure was in the following order (IC50 (nM): concentration for 50% growth inhibition); SA (0.05) > A (0.3) > B2 (1.5) > B1 (3.0) > C2 (20) > C1 (40). Average minimum inhibitory concentrations (MICs) of duocarmycins against microorganisms showed essentially the same ranking order as that of cytotoxicity. There was a large difference between SA and A in their stability in aqueous solvents. For halogenated seco-compounds, a good correlation was found between their cytotoxicities in vitro and their conversion rate to duocarmycin A, suggesting that halogenated seco-compounds undergo closure to the spirocyclopropylhexadienone structure, the pertinent active form, in cells.

Catalog	Product Name	CAS
BADC-00811	Duocarmycin DM free base	1116745-06-2
BADC-00337	Seco-Duocarmycin TM	1142188-60-0
BADC-00223	Duocarmycin A	118292-34-5
BADC-00341	Seco-Duocarmycin SA	152785-82-5
BADC-00605	Duocarmycin TM	157922-77-5
BADC-00332	Seco-DuocarmycinCN	1613286-54-6
BADC-00333	Seco-DuocarmycinDMG	1613286-55-7
BADC-00342	Seco-Duocarmycin MA	1613286-57-9
BADC-00609	Duocarmycin MB	1613286-58-0
BADC-00336	Seco-Duocamycin GA	1613286-59-1

What is Duocarmycin B1?

Duocarmycin B1 is a DNA-alkylating cytotoxin used as a payload in ADC research. It binds to the minor groove of DNA, causing irreversible alkylation and apoptosis. Its high potency makes it suitable for targeted therapeutic development in oncology studies.

14/12/2022

We are interested in how Duocarmycin B1 works in ADC applications.

Duocarmycin B1, when conjugated to antibodies, selectively enters cancer cells and alkylates DNA. This leads to strand breaks and apoptotic cell death, enabling researchers to design effective ADCs with precise cytotoxic activity against tumor cells.

21/4/2022

Could you kindly explain the main research uses of Duocarmycin B1?

Duocarmycin B1 is primarily employed in preclinical ADC studies to evaluate DNA-targeting payloads, assess linker-payload stability, and optimize intracellular delivery strategies, aiding in the design of next-generation targeted therapeutics.

9/8/2022

What chemical characteristics define Duocarmycin B1?

Duocarmycin B1 is a highly potent small molecule with a DNA-alkylating moiety that binds the minor groove. Its chemical structure allows conjugation to antibodies while maintaining cytotoxicity, facilitating use in ADC research applications.

9/9/2016

Dear team, what safety measures should be followed for Duocarmycin B1?

Duocarmycin B1 is extremely cytotoxic, requiring stringent laboratory safety. Proper PPE, fume hood use, and waste management protocols are essential to ensure safe handling during conjugation and ADC experimentation.

29/10/2016

— Dr. Kevin Wallace, Senior Scientist (USA)

Duocarmycin B1 from BOC Sciences arrived with outstanding purity and stability.

9/8/2022

— Dr. Richard Allen, Senior Scientist (UK)

Duocarmycin B1 arrived with clear analytical validation, giving us confidence to proceed in our cytotoxic payload assays.

29/10/2016

— Ms. Anna Keller, Medicinal Chemist (Germany)

The compound’s stability under our experimental conditions was impressive, making Duocarmycin B1 a valuable tool.

9/9/2016

— Dr. Patricia Green, Oncology Researcher (USA)

BOC Sciences’ Duocarmycin B1 supported seamless integration into ADC conjugation workflows, thanks to its reproducibility.