Alsterpaullone
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MedKoo CAT#: 206619

CAS#: 237430-03-4

Description: Alsterpaullone, also known as 9-Nitropaullone and NSC 705701, is a derivative of kenpaullone and an ATP-competitive inhibitor of several cyclin-dependent kinases (CDKs) as well as glycogen synthase kinase 3β (GSK3β). Alsterpaullone induces apoptosis by activation of caspase-9 due to perturbation in mitochondrial membrane potential. Alsterpaullone mediated toxicity in HeLa Cells through Apoptosis-Inducing Effect.


Chemical Structure

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Alsterpaullone
CAS# 237430-03-4

Theoretical Analysis

MedKoo Cat#: 206619
Name: Alsterpaullone
CAS#: 237430-03-4
Chemical Formula: C16H11N3O3
Exact Mass: 293.08
Molecular Weight: 293.282
Elemental Analysis: C, 65.53; H, 3.78; N, 14.33; O, 16.37

Price and Availability

Size Price Availability Quantity
50mg USD 550
100mg USD 950
200mg USD 1650
500mg USD 3250 2 Weeks
1g USD 5250 2 Weeks
2g USD 7450 2 Weeks
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Synonym: 9-Nitropaullone; NSC 705701; NSC705701; NSC-705701; Alsterpaullone

IUPAC/Chemical Name: 7,12-dihydro-9-nitro-indolo[3,2-d][1]benzazepin-6(5H)-one

InChi Key: OLUKILHGKRVDCT-UHFFFAOYSA-N

InChi Code: InChI=1S/C16H11N3O3/c20-15-8-12-11-7-9(19(21)22)5-6-14(11)18-16(12)10-3-1-2-4-13(10)17-15/h1-7,18H,8H2,(H,17,20)

SMILES Code: O=C1NC2=CC=CC=C2C(NC3=C4C=C([N+]([O-])=O)C=C3)=C4C1

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: >2 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:

Product Data:
Biological target: Alsterpaullone (9-Nitropaullone) is a CDK inhibitor, with IC50s of 35 nM, 15 nM, 200 nM and 40 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E and CDK5/p35, respectively. Alsterpaullone also competes with ATP for binding to GSK-3alpha/GSK-3beta with IC50s of both 4 nM.
In vitro activity: The MTT assay indicated that MPP+ induced a dose-dependent decrease of the cell viability, and the cell viability decreased almost 45% at an exposure to 500 μM MPP+ (Figure 1A). However, the cell viability of SH-SY5Y cells exhibited an increase when cells were pretreated with various concentrations of Als (Alsterpaullone) (0.5, 1.0, 2.0 μM) for 24 h before MPP+= treatment (Figure 1B). Moreover, Als (0.25 μM or 0.5 μM) was applied to SH-SY5Y cells treated with MPP+ and the cell viability was assessed 0 h, 12 h, 24 h or 48 h later. The results indicated that the decrease of cell viability induced by MPP+ could be abrogated by 0.5 μM and 24 h Als treatment (Supplementary Figure S1). Reference: Front Cell Neurosci. 2018; 12: 283. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127625/
In vivo activity: To analyze the in vivo effects of alsterpaullone, this study used a mouse model of EBV‐LPD. Viral DNA levels in the peripheral blood of the treatment group decreased compared with nontreated controls (Figure 4B). Moreover, the survival rate significantly increased following treatment with the inhibitor (Figure 4C). Tumor formation in the pancreas was suppressed by inhibitor treatment (Figure 4D). The H&E staining of tumor tissue sections showed a clear reduction in lymphocyte infiltration in inhibitor‐treated mice (Figure 4D). The EBV‐positive B cell infiltration was decreased in mice treated with the inhibitor (Figure 4D). BZLF1, a representative marker of lytic infection and the master key gene for promoting the lytic cycle, was detected in the tumor tissue of nontreated control mice (Figure 4D). These results indicated that the CDK inhibitor has an antitumor effect in an EBV‐LPD mouse model. Reference: Cancer Sci. 2020 Jan; 111(1): 279–287. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942432/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 12.3 42.04
DMSO:PBS (pH 7.2) (1:1) 0.5 1.70
DMF 3.0 10.23

Preparing Stock Solutions

The following data is based on the product molecular weight 293.28 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.

Recalculate based on batch purity %
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. Wang J, Li Y, Gao L, Yan F, Gao G, Li L. GSK-3β Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells. Front Cell Neurosci. 2018 Aug 30;12:283. doi: 10.3389/fncel.2018.00283. PMID: 30233322; PMCID: PMC6127625. 2. Faria CC, Agnihotri S, Mack SC, Golbourn BJ, Diaz RJ, Olsen S, Bryant M, Bebenek M, Wang X, Bertrand KC, Kushida M, Head R, Clark I, Dirks P, Smith CA, Taylor MD, Rutka JT. Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma. Oncotarget. 2015 Aug 28;6(25):21718-29. doi: 10.18632/oncotarget.4304. PMID: 26061748; PMCID: PMC4673298. 3. Watanabe T, Sato Y, Masud HMAA, Takayama M, Matsuda H, Hara Y, Yanagi Y, Yoshida M, Goshima F, Murata T, Kimura H. Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders. Cancer Sci. 2020 Jan;111(1):279-287. doi: 10.1111/cas.14241. Epub 2019 Dec 11. PMID: 31743514; PMCID: PMC6942432. 4. Yin P, Zheng N, Dong J, Xu C, Zhang X, Ding G. Alsterpaullone induces apoptosis of HepG2 cells via a p38 mitogen-activated protein kinase signaling pathway. Oncol Lett. 2019 Jan;17(1):1177-1183. doi: 10.3892/ol.2018.9700. Epub 2018 Nov 14. PMID: 30655881; PMCID: PMC6312958.
In vitro protocol: 1. Wang J, Li Y, Gao L, Yan F, Gao G, Li L. GSK-3β Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells. Front Cell Neurosci. 2018 Aug 30;12:283. doi: 10.3389/fncel.2018.00283. PMID: 30233322; PMCID: PMC6127625. 2. Faria CC, Agnihotri S, Mack SC, Golbourn BJ, Diaz RJ, Olsen S, Bryant M, Bebenek M, Wang X, Bertrand KC, Kushida M, Head R, Clark I, Dirks P, Smith CA, Taylor MD, Rutka JT. Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma. Oncotarget. 2015 Aug 28;6(25):21718-29. doi: 10.18632/oncotarget.4304. PMID: 26061748; PMCID: PMC4673298.
In vivo protocol: 1. Watanabe T, Sato Y, Masud HMAA, Takayama M, Matsuda H, Hara Y, Yanagi Y, Yoshida M, Goshima F, Murata T, Kimura H. Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders. Cancer Sci. 2020 Jan;111(1):279-287. doi: 10.1111/cas.14241. Epub 2019 Dec 11. PMID: 31743514; PMCID: PMC6942432. 2. Yin P, Zheng N, Dong J, Xu C, Zhang X, Ding G. Alsterpaullone induces apoptosis of HepG2 cells via a p38 mitogen-activated protein kinase signaling pathway. Oncol Lett. 2019 Jan;17(1):1177-1183. doi: 10.3892/ol.2018.9700. Epub 2018 Nov 14. PMID: 30655881; PMCID: PMC6312958.

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1: Cui C, Wang Y, Wang Y, Zhao M, Peng S. Alsterpaullone, a Cyclin-Dependent Kinase Inhibitor, Mediated Toxicity in HeLa Cells through Apoptosis-Inducing Effect. J Anal Methods Chem. 2013;2013:602091. doi: 10.1155/2013/602091. Epub 2013 Mar 12. PMID: 23577282; PMCID: PMC3610382.


2: Faria CC, Agnihotri S, Mack SC, Golbourn BJ, Diaz RJ, Olsen S, Bryant M, Bebenek M, Wang X, Bertrand KC, Kushida M, Head R, Clark I, Dirks P, Smith CA, Taylor MD, Rutka JT. Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma. Oncotarget. 2015 Aug 28;6(25):21718-29. doi: 10.18632/oncotarget.4304. PMID: 26061748; PMCID: PMC4673298.


3: Yin P, Zheng N, Dong J, Xu C, Zhang X, Ding G. Alsterpaullone induces apoptosis of HepG2 cells via a p38 mitogen-activated protein kinase signaling pathway. Oncol Lett. 2019 Jan;17(1):1177-1183. doi: 10.3892/ol.2018.9700. Epub 2018 Nov 14. PMID: 30655881; PMCID: PMC6312958.


4: Watanabe T, Sato Y, Masud HMAA, Takayama M, Matsuda H, Hara Y, Yanagi Y, Yoshida M, Goshima F, Murata T, Kimura H. Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders. Cancer Sci. 2020 Jan;111(1):279-287. doi: 10.1111/cas.14241. Epub 2019 Dec 11. PMID: 31743514; PMCID: PMC6942432.


5: Wang J, Li Y, Gao L, Yan F, Gao G, Li L. GSK-3β Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells. Front Cell Neurosci. 2018 Aug 30;12:283. doi: 10.3389/fncel.2018.00283. PMID: 30233322; PMCID: PMC6127625.


6: Greenwald RB, Zhao H, Xia J, Wu D, Nervi S, Stinson SF, Majerova E, Bramhall C, Zaharevitz DW. Poly(ethylene glycol) prodrugs of the CDK inhibitor, alsterpaullone (NSC 705701): synthesis and pharmacokinetic studies. Bioconjug Chem. 2004 Sep-Oct;15(5):1076-83. doi: 10.1021/bc049906a. PMID: 15366962.


7: Lahusen T, De Siervi A, Kunick C, Senderowicz AM. Alsterpaullone, a novel cyclin-dependent kinase inhibitor, induces apoptosis by activation of caspase-9 due to perturbation in mitochondrial membrane potential. Mol Carcinog. 2003 Apr;36(4):183-94. doi: 10.1002/mc.10114. PMID: 12669310.


8: Kunick C, Zeng Z, Gussio R, Zaharevitz D, Leost M, Totzke F, Schächtele C, Kubbutat MH, Meijer L, Lemcke T. Structure-aided optimization of kinase inhibitors derived from alsterpaullone. Chembiochem. 2005 Mar;6(3):541-9. doi: 10.1002/cbic.200400099. PMID: 15696597.


9: Walters BJ, Lin W, Diao S, Brimble M, Iconaru LI, Dearman J, Goktug A, Chen T, Zuo J. High-throughput screening reveals alsterpaullone, 2-cyanoethyl as a potent p27Kip1 transcriptional inhibitor. PLoS One. 2014 Mar 19;9(3):e91173. doi: 10.1371/journal.pone.0091173. PMID: 24646893; PMCID: PMC3960108.


10: Martín-Hidalgo D, Bragado MJ, García-Marín LJ, Gil Anaya MC. Supplementation of freezing/thawing media with GSK3 inhibitor alsterpaullone does not bypass the harmful effect of cryopreservation on boar spermatozoa. Anim Reprod Sci. 2018 Sep;196:176-183. doi: 10.1016/j.anireprosci.2018.08.002. Epub 2018 Aug 6. PMID: 30097318.


11: Trevino M, Stefanik DJ, Rodriguez R, Harmon S, Burton PM. Induction of canonical Wnt signaling by alsterpaullone is sufficient for oral tissue fate during regeneration and embryogenesis in Nematostella vectensis. Dev Dyn. 2011 Dec;240(12):2673-9. doi: 10.1002/dvdy.22774. Epub 2011 Nov 2. PMID: 22052821; PMCID: PMC3672222.


12: Guendel I, Agbottah ET, Kehn-Hall K, Kashanchi F. Inhibition of human immunodeficiency virus type-1 by cdk inhibitors. AIDS Res Ther. 2010 Mar 24;7(1):7. doi: 10.1186/1742-6405-7-7. PMID: 20334651; PMCID: PMC2852372.


13: Soni DV, Jacobberger JW. Inhibition of cdk1 by alsterpaullone and thioflavopiridol correlates with increased transit time from mid G2 through prophase. Cell Cycle. 2004 Mar;3(3):349-57. Epub 2004 Mar 1. PMID: 14726692.


14: Lee HW, Arif E, Altintas MM, Quick K, Maheshwari S, Plezia A, Mahmood A, Reiser J, Nihalani D, Gupta V. High-content screening assay-based discovery of paullones as novel podocyte-protective agents. Am J Physiol Renal Physiol. 2018 Feb 1;314(2):F280-F292. doi: 10.1152/ajprenal.00338.2017. Epub 2017 Oct 18. PMID: 29046299; PMCID: PMC5866451.


15: Bae T, Weon KY, Lee JW, Eum KH, Kim S, Choi JW. Restoration of paclitaxel resistance by CDK1 intervention in drug-resistant ovarian cancer. Carcinogenesis. 2015 Dec;36(12):1561-71. doi: 10.1093/carcin/bgv140. Epub 2015 Oct 6. PMID: 26442525.


16: Taubenheim J, Willoweit-Ohl D, Knop M, Franzenburg S, He J, Bosch TCG, Fraune S. Bacteria- and temperature-regulated peptides modulate β-catenin signaling in Hydra. Proc Natl Acad Sci U S A. 2020 Sep 1;117(35):21459-21468. doi: 10.1073/pnas.2010945117. Epub 2020 Aug 19. PMID: 32817436; PMCID: PMC7474684.


17: Zahler S, Liebl J, Fürst R, Vollmar AM. Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro. Angiogenesis. 2010 Sep;13(3):239-49. doi: 10.1007/s10456-010-9181-1. Epub 2010 Aug 13. PMID: 20706783.


18: Lommel M, Strompen J, Hellewell AL, Balasubramanian GP, Christofidou ED, Thomson AR, Boyle AL, Woolfson DN, Puglisi K, Hartl M, Holstein TW, Adams JC, Özbek S. Hydra Mesoglea Proteome Identifies Thrombospondin as a Conserved Component Active in Head Organizer Restriction. Sci Rep. 2018 Aug 6;8(1):11753. doi: 10.1038/s41598-018-30035-2. PMID: 30082916; PMCID: PMC6079037.


19: Shi G, Scott H, Azhar NIFM, Gialeli A, Clennell B, Lee KS, Hurcombe J, Whitcomb D, Coward R, Wong LF, Cordero-Llana O, Uney JB. AZD5438 a GSK-3a/b and CDK inhibitor is antiapoptotic modulates mitochondrial activity and protects human neurons from mitochondrial toxins. Sci Rep. 2023 May 23;13(1):8334. doi: 10.1038/s41598-023-35480-2. PMID: 37221196; PMCID: PMC10205901.


20: Xu Y, Kong J, Hu P. Computational Drug Repurposing for Alzheimer's Disease Using Risk Genes From GWAS and Single-Cell RNA Sequencing Studies. Front Pharmacol. 2021 Jun 30;12:617537. doi: 10.3389/fphar.2021.617537. PMID: 34276354; PMCID: PMC8277916.