OT-82 | CAS#1800487-55-1 | NAMPT Inhibitor

MedKoo Cat#: 207115 | Name: OT-82

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

OT-82 is a potent NAMPT Inhibitor that targets the strong dependence of hematological malignancies on NAD biosynthesis. OT-82 showed strong efficacy against hematopoietic malignancies including acute myeloblastic and lymphoblastic adult and pediatric leukemias, erythroleukemia, multiple myeloma, and Burkitt's lymphoma in vitro and in mouse xenograft models.

Chemical Structure

OT-82

CAS#1800487-55-1 (free base)

Theoretical Analysis

MedKoo Cat#: 207115

Name: OT-82

CAS#: 1800487-55-1 (free base)

Chemical Formula: C26H21FN4O

Exact Mass: 424.1699

Molecular Weight: 424.48

Elemental Analysis: C, 73.57; H, 4.99; F, 4.48; N, 13.20; O, 3.77

Price and Availability

Size	Price	Availability
5mg	USD 650.00	2 Weeks
10mg	USD 1,050.00	2 Weeks
25mg	USD 1,950.00	2 Weeks
50mg	USD 2,950.00	2 Weeks
100mg	USD 3,950.00	2 Weeks

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Related CAS #

1800487-55-1 (free base) OT-82 HCl

Synonym

OT-82; OT 82; OT82; NAMPTi OT-82; nicotinamide phosphoribosyl transferase inhibitor OT-82;

IUPAC/Chemical Name

N-(3-(1H-pyrazol-4-yl)propyl)-3-((4-fluorophenyl)ethynyl)-4-(pyridin-4-yl)benzamide

InChi Key

CEPAXRIKSUXHHB-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H21FN4O/c27-24-8-4-19(5-9-24)3-6-22-16-23(7-10-25(22)21-11-14-28-15-12-21)26(32)29-13-1-2-20-17-30-31-18-20/h4-5,7-12,14-18H,1-2,13H2,(H,29,32)(H,30,31)

SMILES Code

O=C(C1=CC(C#CC2=CC=C(C=C2)F)=C(C=C1)C3=CC=NC=C3)NCCCC4=CNN=C4

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

More Info

OT-82 binds to and inhibits the activity of NAMPT. This depletes cellular NAD and inhibits NAD-dependent enzymes, both of which are needed for rapid cell proliferation; this results in cell death in NAMPT-overexpressing cancer cells. NAMPT, an enzyme that is responsible for maintaining the intracellular NAD pool, plays a key role in the regulation of cellular metabolism and has cytokine-like activities. NAMPT is overexpressed in a variety of cancers and metabolic disorders; tumor cells rely on NAMPT activity for their NAD supply

Product Data

Product Data

Instruction

View handling instruction

Biological target:

OT-82 is a potent, selective and orally active inhibitor of NAMPT.

In vitro activity:

OT-82 decreased NAD concentration and impaired proliferation of EWS cells in a dose-dependent manner, with IC50 values in the single-digit nanomolar range. Notably, genetic depletion of NAMPT phenocopied pharmacological inhibition. On-target activity of OT-82 was confirmed with the addition of NMN, the product of NAMPT, which rescued NAD concentration and EWS cellular viability. Mechanistically, OT-82 treatment resulted in impaired DNA damage repair through loss of PARP activity, G2 cell-cycle arrest, and apoptosis in EWS cells. Reference: Oncogenesis. 2020 Sep 10;9(9):80. https://pubmed.ncbi.nlm.nih.gov/32908120/

In vivo activity:

Oral treatment of engrafted mice with a previously optimized administration scheme of OT-82(Korotchkina L. et al.) was well tolerated as indicated by low percentages of weight loss (Supplementary Table 3). When combining the efficacy data of OT-82 on these 19 additional PDXs with the previously reported data on two PDXs, OT-82 significantly extended the survival of all but one PDX (20/21, 95%). The extension of event-free survival (EFS) by OT-82 treatment, T-C (EFS OT-82-treated (T) - EFS control-treated cohort (C)), ranged from 10.9 to 73.6 days and T/C values varied from 2.4 to 10.7 (Figure 3A–C, Table 1, Supplementary Table 3). Reference: Leukemia. 2020 Jun;34(6):1524-1539. https://pubmed.ncbi.nlm.nih.gov/31848452/

	Solvent	mg/mL	mM
Solubility
	DMSO	92.5	217.91
	Ethanol	85.0	200.25

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 424.48 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.

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. Gibson AE, Yeung C, Issaq SH, Collins VJ, Gouzoulis M, Zhang Y, Ji J, Mendoza A, Heske CM. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) with OT-82 induces DNA damage, cell death, and suppression of tumor growth in preclinical models of Ewing sarcoma. Oncogenesis. 2020 Sep 10;9(9):80. doi: 10.1038/s41389-020-00264-0. PMID: 32908120; PMCID: PMC7481307. 2. Korotchkina L, Kazyulkin D, Komarov PG, Polinsky A, Andrianova EL, Joshi S, Gupta M, Vujcic S, Kononov E, Toshkov I, Tian Y, Krasnov P, Chernov MV, Veith J, Antoch MP, Middlemiss S, Somers K, Lock RB, Norris MD, Henderson MJ, Haber M, Chernova OB, Gudkov AV. OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis. Leukemia. 2020 Jul;34(7):1828-1839. doi: 10.1038/s41375-019-0692-5. Epub 2020 Jan 2. PMID: 31896781; PMCID: PMC7326709. 3. Somers K, Evans K, Cheung L, Karsa M, Pritchard T, Kosciolek A, Bongers A, El-Ayoubi A, Forgham H, Middlemiss S, Mayoh C, Jones L, Gupta M, Kees UR, Chernova O, Korotchkina L, Gudkov AV, Erickson SW, Teicher B, Smith MA, Norris MD, Haber M, Lock RB, Henderson MJ. Effective targeting of NAMPT in patient-derived xenograft models of high-risk pediatric acute lymphoblastic leukemia. Leukemia. 2020 Jun;34(6):1524-1539. doi: 10.1038/s41375-019-0683-6. Epub 2019 Dec 17. PMID: 31848452; PMCID: PMC9110273.

In vitro protocol:

In vivo protocol:

1: Messana VG, Fascì A, Vitale N, Micillo M, Rovere M, Pesce NA, Martines C, Efremov DG, Vaisitti T, Deaglio S. A molecular circuit linking the BCR to the NAD biosynthetic enzyme NAMPT is an actionable target in Richter syndrome. Blood Adv. 2024 Apr 23;8(8):1920-1933. doi: 10.1182/bloodadvances.2023011690. PMID: 38359376; PMCID: PMC11021907. 2: McKay-Corkum GB, Collins VJ, Yeung C, Ito T, Issaq SH, Holland D, Vulikh K, Zhang Y, Lee U, Lei H, Mendoza A, Shern JF, Yohe ME, Yamamoto K, Wilson K, Ji J, Karim BO, Thomas CJ, Krishna MC, Neckers LM, Heske CM. Inhibition of NAD+-Dependent Metabolic Processes Induces Cellular Necrosis and Tumor Regression in Rhabdomyosarcoma Models. Clin Cancer Res. 2023 Nov 1;29(21):4479-4491. doi: 10.1158/1078-0432.CCR-23-0200. PMID: 37616468; PMCID: PMC10841338. 3: Wei Y, Xiang H, Zhang W. Review of various NAMPT inhibitors for the treatment of cancer. Front Pharmacol. 2022 Sep 7;13:970553. doi: 10.3389/fphar.2022.970553. PMID: 36160449; PMCID: PMC9490061. 4: Gibson AE, Yeung C, Issaq SH, Collins VJ, Gouzoulis M, Zhang Y, Ji J, Mendoza A, Heske CM. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) with OT-82 induces DNA damage, cell death, and suppression of tumor growth in preclinical models of Ewing sarcoma. Oncogenesis. 2020 Sep 10;9(9):80. doi: 10.1038/s41389-020-00264-0. PMID: 32908120; PMCID: PMC7481307. 5: Korotchkina L, Kazyulkin D, Komarov PG, Polinsky A, Andrianova EL, Joshi S, Gupta M, Vujcic S, Kononov E, Toshkov I, Tian Y, Krasnov P, Chernov MV, Veith J, Antoch MP, Middlemiss S, Somers K, Lock RB, Norris MD, Henderson MJ, Haber M, Chernova OB, Gudkov AV. OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis. Leukemia. 2020 Jul;34(7):1828-1839. doi: 10.1038/s41375-019-0692-5. Epub 2020 Jan 2. PMID: 31896781; PMCID: PMC7326709. 6: Somers K, Evans K, Cheung L, Karsa M, Pritchard T, Kosciolek A, Bongers A, El-Ayoubi A, Forgham H, Middlemiss S, Mayoh C, Jones L, Gupta M, Kees UR, Chernova O, Korotchkina L, Gudkov AV, Erickson SW, Teicher B, Smith MA, Norris MD, Haber M, Lock RB, Henderson MJ. Effective targeting of NAMPT in patient- derived xenograft models of high-risk pediatric acute lymphoblastic leukemia. Leukemia. 2020 Jun;34(6):1524-1539. doi: 10.1038/s41375-019-0683-6. Epub 2019 Dec 17. PMID: 31848452; PMCID: PMC9110273.