Name: MMAD
Brand: BOC Sciences
Price: 568 USD
Availability: MadeToOrder

Synonyms

Demethyldolastatin 10; Monomethylauristatin D; Monomethyl Dolastatin 10

IUPAC Name

(2S)-N-[(2S)-1-[[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamide

Canonical SMILES

CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(CC2=CC=CC=C2)C3=NC=CS3)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)NC

InChI

InChI=1S/C41H66N6O6S/c1-12-27(6)36(46(9)41(51)35(26(4)5)45-39(50)34(42-8)25(2)3)32(52-10)24-33(48)47-21-16-19-31(47)37(53-11)28(7)38(49)44-30(40-43-20-22-54-40)23-29-17-14-13-15-18-29/h13-15,17-18,20,22,25-28,30-32,34-37,42H,12,16,19,21,23-24H2,1-11H3,(H,44,49)(H,45,50)/t27-,28+,30-,31-,32+,34-,35-,36-,37+/m0/s1

InChIKey

BLUGYPPOFIHFJS-UUFHNPECSA-N

Density

1.1±0.1 g/cm3

Solubility

Soluble in DMSO, not in water

Flash Point

501.8±34.3 °C

Index Of Refraction

1.537

Vapor Pressure

0.0±0.3 mmHg at 25°C

Appearance

White to off-white solid

Shipping

Room temperature

Storage

Dry, dark and at 0 - 4 °C for short term (days to weeks) or -20 °C for long term (months to years).

Boiling Point

906.1±65.0 °C at 760 mmHg

In Vitro

MMAD (Monomethyl Dolastatin 10) is coupled through a stable oxime-ligation process to yield several near-homogenous antibody-drug conjugates (ADCs) with a drug-to-antibody ratio of ~2.0. The resulting conjugates demonstrate good pharmacokinetic properties, potent in vitro cytotoxic activity against HER2+ cancer cells. When compared with ADCs prepared by cysteine alkylation following native interchain disulfide reduction, site-specific unnatural-amino-acid-based ADCs are shown to have increased in vitro cytotoxicity.

MMAD (Monomethyl Auristatin D) is a synthetic derivative of dolastatin 10 and a highly potent ADC cytotoxin commonly used as an ADC payload in antibody-drug conjugates. MMAD exerts its cytotoxic effects by binding to tubulin and inhibiting microtubule polymerization, leading to mitotic arrest and apoptosis in rapidly proliferating tumor cells. Its strong antimitotic activity makes it a valuable payload for targeted oncology therapeutics.

In the design of antibody-drug conjugates, MMAD is typically conjugated to monoclonal antibodies via stable or cleavable linker technologies. These linkers ensure that the payload remains inactive in circulation and is released only upon ADC internalization and lysosomal processing within cancer cells. The selective delivery mechanism enhances tumor specificity, reduces systemic toxicity, and allows for potent antitumor activity even at low drug-to-antibody ratios (DARs), which is critical for ADC therapeutic efficacy.

Applications of MMAD include its use in preclinical and clinical ADC candidates targeting both hematologic malignancies and solid tumors, such as lymphoma, multiple myeloma, breast cancer, and lung cancer. Its compatibility with diverse linker chemistries, predictable pharmacokinetics, and high cytotoxic potency make MMAD an ideal choice for ADC research and development. Researchers often employ MMAD to optimize ADC design, evaluate linker stability, and study tumor-selective payload delivery in next-generation antibody-drug conjugates.

1.Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery.

Li X;Vogt FG;Hayes D Jr;Mansour HM Eur J Pharm Sci. 2014 Feb 14;52:191-205. doi: 10.1016/j.ejps.2013.10.016. Epub 2013 Nov 9.

The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides, respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morphology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (<10 μm) with smaller MMAD values for SD AZI powders in contrast to SD TOB powders. Positive linear correlations were observed between the aerosol dispersion performance parameter of FPF with increasing spray-drying pump rates and also with the difference between thermal parameters expressed as Tg-To (i.

2.Evaluation of the developmental toxicity of ethylene glycol aerosol in CD-1 mice by nose-only exposure.

Tyl RW;Ballantyne B;Fisher LC;Fait DL;Dodd DE;Klonne DR;Pritts IM;Losco PE Fundam Appl Toxicol. 1995 Aug;27(1):49-62.

Ethylene glycol (EG; CAS No. 107-21-1) is teratogenic to mice by whole-body (WB) exposure to aerosol (1000-2500 mg/m3). The WB results were confounded by possible exposure from ingestion after grooming and/or from percutaneous absorption. Therefore, CD-1 mice were exposed to EG aerosol (MMAD 2.6 +/- 1.7 microns) on Gestational Days (GD) 6 through 15, 6 hr/day, by nose-only (NO) (0, 500, 1000, or 2500 mg/m3) or WB exposures (0 or 2100 mg/m3, as positive control), 30/group. Five additional "satellite" females each at 2500 mg/m3 NO and 2100 mg/m3 WB were exposed on GD 6 for measurement of EG on fur. Control environments were water aerosol (4200 mg/m3 for NO; 2700 mg/m3 for WB). Females were weighed and evaluated for clinical signs and water consumption throughout gestation. On GD 18, maternal uterus, liver, and kidneys (2) were weighed, with kidneys examined microscopically. Corpora lutea and implantation sites were recorded. Live fetuses were weighed, sexed, and examined for structural alterations. For NO dams, kidney weights were increased at 1000 and 2500 mg/m3; no renal lesions and no other treatment-related maternal toxicity were observed. There were no effects on pre- or postimplantation loss; fetal body weights/litter were reduced at 2500 mg/m3.

3.Dual pathway clearance of 99mTc-DTPA from the bronchial mucosa.

Bennett WD;Ilowite JS Am Rev Respir Dis. 1989 May;139(5):1132-8.

Many studies have reported clearance rates of 99mTc-DTPA from the alveolar epithelial surface, but few have measured clearance of this solute from the bronchial mucosa. Those that have attempted such measurements have discounted the possibility that 99mTc-DTPA may be removed from the bronchial airways by mucocilliary transport as well as by absorption through the epithelium. This study was designed to better approximate the rate of 99mTc-DTPA absorption across the bronchial epithelium by correcting the measurements of total 99mTc-DTPA clearance for mucus transport. On two separate study days, each normal, nonsmoking subject (n = 8) breathed an aqueous aerosol (2.0 microns MMAD, sigma g = 2.0) containing 99mTc bound to DTPA or human serum ablumin (HSA) (a relatively nonpermeable solute that is cleared only by mucus transport over the period of measured clearance) while seated in front of a gamma camera. Breathing pattern was standardized to produce a similar central deposition of particles on both study days. From measurements of retention versus time over a 1-h period, exponential rate constants (Ktot and Km) were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively.

What is MMAD?

MMAD (Monomethyl auristatin D) is a synthetic cytotoxic agent used as a payload in ADC research. It targets tubulin to inhibit microtubule formation, providing potent cytotoxic effects for targeted delivery studies in experimental cancer models.

10/4/2018

We would like to know how MMAD functions in ADCs.

MMAD is delivered via antibody conjugation to specific cell targets. After internalization, it disrupts microtubule dynamics, leading to cell cycle arrest and apoptosis, enabling selective cytotoxic activity in research applications.

24/8/2019

We would like to know what types of linkers are suitable for MMAD.

MMAD can be conjugated using cleavable or non-cleavable linkers, including peptide or thioether chemistries. Proper linker selection influences ADC stability, payload release, and cytotoxic efficiency.

8/12/2019

May I ask if BOC Sciences is able to customize MMAD ADCs?

BOC Sciences provides tailored ADC synthesis using MMAD, offering services from linker selection and conjugation optimization to analytical validation, supporting preclinical and laboratory research needs.

24/2/2017

Good afternoon! Could you advise on the recommended storage conditions for MMAD?

MMAD should be stored according to BOC Sciences guidelines, typically at low temperature and protected from light, to preserve chemical integrity and ensure consistent performance in ADC development experiments.

26/8/2018

— Dr. Peter Hall, Senior Scientist (USA)

MMAD provided by BOC Sciences showed high purity and stability, enabling accurate cytotoxicity assays.

8/12/2019

— Dr. Sophia Wright, ADC Chemist (UK)

Excellent support and fast delivery. MMAD met our analytical and regulatory requirements.

26/8/2018

— Dr. Thomas Weber, Medicinal Chemist (Germany)

Reliable batch consistency and professional technical guidance. MMAD enhanced our ADC studies.

24/2/2017

— Dr. Emily Scott, Biochemist (Canada)

Prompt shipment and high-quality compound. MMAD supported our in vitro experiments smoothly.