Name: PNU-159682
Brand: BOC Sciences
Price: 719 USD
Availability: MadeToOrder

Synonyms

(8S,10S)-7,8,9,10-Tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-10-(((1S,3R,4aS,9S,9aR,10aS)-octahydro-9-methoxy-1-methyl-1H-pyrano(4',3':4,5)oxazolo(2,3-c)(1,4)oxazin-3-yl)oxy)-5,12-naphthacenedione; 5,12-Naphthacenedione, 7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-10-(((1S,3R,4aS,9S,9aR,10aS)-octahydro-9-methoxy-1-methyl-1H-pyrano(4',3':4,5)oxazolo(2,3-c)(1,4)oxazin-3-yl)oxy)-, (8S,10S)-; PNU159682; PNU 159682

IUPAC Name

(7S,9S)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-7-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-8,10-dihydro-7H-tetracene-5,12-dione

Canonical SMILES

CC1C2C(CC(O1)OC3CC(CC4=C(C5=C(C(=C34)O)C(=O)C6=C(C5=O)C=CC=C6OC)O)(C(=O)CO)O)N7CCOC(C7O2)OC

InChI

InChI=1S/C32H35NO13/c1-13-29-16(33-7-8-43-31(42-3)30(33)46-29)9-20(44-13)45-18-11-32(40,19(35)12-34)10-15-22(18)28(39)24-23(26(15)37)25(36)14-5-4-6-17(41-2)21(14)27(24)38/h4-6,13,16,18,20,29-31,34,37,39-40H,7-12H2,1-3H3/t13-,16-,18-,20-,29+,30+,31-,32-/m0/s1

InChIKey

SLURUCSFDHKXFR-WWMWMSKMSA-N

Density

1.58±0.1 g/cm3 (Predicted)

Solubility

Soluble in DMSO, chloroform (slightly), methanol (slightly)

Flash Point

460.9±34.3 °C

Index Of Refraction

1.691

PSA

190.75000

Vapor Pressure

0.0±3.2 mmHg at 25°C

Appearance

White solid powder

Shelf Life

≥12 months if stored properly

Shipping

Room temperature

Storage

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

Boiling Point

838.5±65.0 °C at 760 mmHg

In Vitro

PNU-159682 inhibits a panel of human tumor cell lines with IC70 values in the range of 0.07-0.58 nM, and is 2,360- to 790-fold and 6,420- to 2,100-fold more potent than MMDX and doxorubicin, respectively. PNU-159682 (100 μM) weakly inhibits topoisomerase II unknotting activity. PNU-159682 (10 μM)-DNA adducts contain one or two drug molecules bound to double-stranded DNA. PNU-159682 shows cytotoxic effect on CAIX-expressing SKRC-52 cells with IC50 of 25 nM.

In Vivo

PNU-159682 (15 μg/kg, i.v.) shows antitumor activity in mice bearing disseminated murine L1210 leukemia and in MX-1 human mammary carcinoma xenografts at 4 μg/kg. PNU-159682 (25 nmol/kg) exhibits a potent antitumor effect in mice bearing SKRC-52 xenografted tumors.

PNU-159682 is an exceptionally potent anthracycline derivative and a notable ADC cytotoxin with wide potential as an ADC payload for antibody-drug conjugates. It exhibits cytotoxic activity several hundred times stronger than its parent compound, doxorubicin, making it a powerful candidate for targeted cancer therapies. Its mechanism involves intercalation into DNA and inhibition of topoisomerase II, leading to double-strand DNA breaks and irreversible apoptosis in rapidly dividing tumor cells.

In the context of antibody-drug conjugates, PNU-159682 is conjugated to monoclonal antibodies via optimized linker systems, ensuring stability in systemic circulation while enabling controlled release inside tumor cells. The extraordinary potency of this payload allows effective therapeutic activity even at very low drug-to-antibody ratios (DARs), which is critical for maintaining safety while maximizing efficacy. By combining antibody specificity with the DNA-damaging mechanism of PNU-159682, ADCs can overcome resistance often seen with conventional chemotherapies.

Applications of PNU-159682 include its role in the design of experimental ADCs targeting hematological cancers, such as leukemias and lymphomas, as well as solid tumors including breast, lung, and ovarian cancers. Its unique pharmacological profile makes it particularly suitable for indications where extreme potency is required to achieve therapeutic benefit. Researchers are also exploring novel linker strategies to optimize conjugation efficiency and tumor-selective release, further broadening the scope of this anthracycline-based payload in ADC drug discovery.

1.In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: a comparison with human liver microsomes.

Quintieri L1, Fantin M, Palatini P, De Martin S, Rosato A, Caruso M, Geroni C, Floreani M. Biochem Pharmacol. 2008 Sep 15;76(6):784-95. doi: 10.1016/j.bcp.2008.07.003. Epub 2008 Jul 11.

We recently demonstrated that nemorubicin (MMDX), an investigational antitumor drug, is converted to an active metabolite, PNU-159682, by human liver cytochrome P450 (CYP) 3A4. The objectives of this study were: (1) to investigate MMDX metabolism by liver microsomes from laboratory animals (mice, rats, and dogs of both sexes) to ascertain whether PNU-159682 is also produced in these species, and to identify the CYP form(s) responsible for its formation; (2) to compare the animal metabolism of MMDX with that by human liver microsomes (HLMs), in order to determine which animal species is closest to human beings; (3) to explore whether differences in PNU-159682 formation are responsible for previously reported species- and sex-related differences in MMDX host toxicity. The animal metabolism of MMDX proved to be qualitatively similar to that observed with HLMs since, in all tested species, MMDX was mainly converted to PNU-159682 by a single CYP3A form.

2.The interaction of nemorubicin metabolite PNU-159682 with DNA fragments d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) shows a strong but reversible binding to G:C base pairs.

Mazzini S1, Scaglioni L, Mondelli R, Caruso M, Sirtori FR. Bioorg Med Chem. 2012 Dec 15;20(24):6979-88. doi: 10.1016/j.bmc.2012.10.033. Epub 2012 Nov 3.

The antitumor anthracycline nemorubicin is converted by human liver microsomes to a major metabolite, PNU-159682 (PNU), which was found to be much more potent than its parent drug toward cultured tumor cells and in vivo tumor models. The mechanism of action of nemorubicin appears different from other anthracyclines and until now is the object of studies. In fact PNU is deemed to play a dominant, but still unclear, role in the in vivo antitumor activity of nemorubicin. The interaction of PNU with the oligonucleotides d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) was studied with a combined use of (1)H and (31)P NMR spectroscopy and by ESI-mass experiments. The NMR studies allowed to establish that the intercalation between the base pairs of the duplex leads to very stable complexes and at the same time to exclude the formation of covalent bonds. Melting experiments monitored by NMR, allowed to observe with high accuracy the behaviour of the imine protons with temperature, and the results showed that the re-annealing occurs after melting.

3.Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes.

Quintieri L1, Geroni C, Fantin M, Battaglia R, Rosato A, Speed W, Zanovello P, Floreani M. Clin Cancer Res. 2005 Feb 15;11(4):1608-17.

PURPOSE: Nemorubicin (3'-deamino-3'-[2''(S)-methoxy-4''-morpholinyl]doxorubicin; MMDX) is an investigational drug currently in phase II/III clinical testing in hepatocellular carcinoma. A bioactivation product of MMDX, 3'-deamino-3'',4'-anhydro-[2''(S)-methoxy-3''(R)-oxy-4''-morpholinyl]doxorubicin (PNU-159682), has been recently identified in an incubate of the drug with NADPH-supplemented rat liver microsomes. The aims of this study were to obtain information about MMDX biotransformation to PNU-159682 in humans, and to explore the antitumor activity of PNU-159682.

HPLC

HNMR

What is PNU-159682?

PNU-159682 is a highly potent anthracycline-derived cytotoxin used as a payload in ADC development. It inhibits DNA replication by intercalating into DNA and forming covalent adducts, offering strong cytotoxicity for targeted therapeutic research.

19/3/2019

We are interested in how PNU-159682 acts in antibody-drug conjugates.

Within ADCs, PNU-159682 is delivered selectively to target cells. Upon internalization and release, it interacts with DNA, blocking replication and triggering cell death, enabling precise cytotoxic action in research models.

2/11/2021

Dear BOC Sciences, which linkers would you recommend for PNU-159682 ADCs?

PNU-159682 can be conjugated using cleavable linkers such as peptide or disulfide linkers. Linker chemistry determines intracellular release efficiency and ADC stability, which are critical for preclinical evaluation.

5/7/2022

May I ask if BOC Sciences supports custom PNU-159682 ADC development?

BOC Sciences provides comprehensive ADC development using PNU-159682, including payload conjugation, linker selection, and analytical support to optimize ADC design for laboratory and preclinical research.

20/5/2020

Dear BOC Sciences, what are the recommended storage considerations for PNU-159682?

PNU-159682 should be stored under controlled conditions as specified by BOC Sciences, typically at low temperature and protected from light, to maintain stability and activity for research and conjugation applications.

18/9/2020

— Dr. Andrew Scott, Senior Scientist (USA)

High-purity PNU-159682 from BOC Sciences enabled accurate cytotoxicity assays. Delivery was prompt and reliable.

5/7/2022

— Dr. Olivia Harris, ADC Chemist (UK)

Technical support was very helpful in understanding conjugation strategies. PNU-159682 met all expectations.

18/9/2020

— Dr. Lars Fischer, Medicinal Chemist (Germany)

Excellent consistency and documentation. BOC Sciences made our ADC project smoother.

20/5/2020

— Dr. Sarah White, Biochemist (Canada)

Fast delivery, high quality, and responsive customer service. PNU-159682 batches were perfect for our assays.