Istradefylline
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MedKoo CAT#: 315137

CAS#: 155270-99-8

Description: Istradefylline (KW-6002) is a selective antagonist at the A2A receptor. It has been found to be useful in the treatment of Parkinson's disease. Istradefylline reduces dyskinesia resulting from long-term treatment with classical antiparkinson drugs such as levodopa. Istradefylline is an analog of caffeine.

Chemical Structure

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Istradefylline
CAS# 155270-99-8
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 315137
Name: Istradefylline
CAS#: 155270-99-8
Chemical Formula: C20H24N4O4
Exact Mass: 384.18
Molecular Weight: 384.430
Elemental Analysis: C, 62.49; H, 6.29; N, 14.57; O, 16.65

Price and Availability

Size Price Availability Quantity
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 750 Ready to ship
1g USD 1250 2 weeks
2g USD 2050 2 weeks
Bulk inquiry

Synonym: KW6002; KW 6002; KW-6002; Istradefylline; Nourianz.

IUPAC/Chemical Name: 8-[(E)-2-(3,4-dimethoxyphenyl)vinyl]-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione

InChi Key: IQVRBWUUXZMOPW-PKNBQFBNSA-N

InChi Code: InChI=1S/C20H24N4O4/c1-6-23-18-17(19(25)24(7-2)20(23)26)22(3)16(21-18)11-9-13-8-10-14(27-4)15(12-13)28-5/h8-12H,6-7H2,1-5H3/b11-9+

SMILES Code: O=C(N1CC)N(CC)C2=C(N(C)C(/C=C/C3=CC=C(OC)C(OC)=C3)=N2)C1=O

Appearance: Light green to green 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:
Product Data
Certificate of Analysis:
View CoA: current batch, Lot#-T7R05C24
Safety Data Sheet (SDS):
View Safety Data Sheet (SDS)
Instruction:
View handling instruction
Biological target: Istradefylline is a very potent, selective and orally active adenosine A2A receptor antagonist with Ki of 2.2 nM in experimental models of Parkinson's disease.
In vitro activity: Istradefylline exhibited high affinity for A2A receptors in humans, marmosets, dogs, rats, and mice. The affinities for the other subtypes of adenosine receptors (A1, A2B, and A3) were lower than that for A2A receptors in each species. Istradefylline demonstrated no significant affinity for other neurotransmitter receptors, including dopamine receptors (D1, D2, D3, D4, and D5). In addition, istradefylline hardly inhibited monoamine oxidase-A, monoamine oxidase-B, or catechol-O-methyl transferase. A kinetic analysis indicated that istradefylline reversibly binds to the human A2A receptors: The association reached equilibrium within 1 min, and the binding was also almost completely dissociated within 1 min. Istradefylline inhibited the A2A agonist CGS21680-induced accumulation of cAMP in the cultured cells and then shifted the concentration-response curve of CGS21680 to the right without affecting the maximal response of the agonist. These results indicate that istradefylline is a potent, selective, and competitive A2A receptor antagonist. Reference: Naunyn Schmiedebergs Arch Pharmacol. 2013 Nov;386(11):963-72. https://dx.doi.org/10.1007/s00210-013-0897-5
In vivo activity: In 14–21-month-old wild-type (WT) nontransgenic mice and hAPP-J20 mice, administration of istradefylline in the drinking water caused dose-dependent increases of drug levels in plasma and brain (Suppl. Fig. 1). In pilot experiments, doses higher than 10 mg/kg/day increased total movements and rearing in both genotypes (Suppl. Fig. 2), consistent with reports that istradefylline enhances locomotion. To avoid this potential confound, mice were treated with 4 or 10 mg/kg/day. The effects of istradefylline on learning and memory were tested with the Morris water maze. hAPP mice treated with 4 or 10 mg/kg/day performed better than vehicle-treated hAPP mice during the first 20 seconds of the probe trial (Fig. 2E; Suppl. Fig. 3C). In a second probe trial 3 days after training, hAPP mice treated with 10 mg/kg/day again showed enhanced performance (Fig. 2G, H). Drug-treated hAPP mice also had faster swim speeds than vehicle-treated hAPP mice (Fig. 2F and I). At 15 mg/kg/day, istradefylline did not affect learning (Suppl. Fig. 5A) but impaired probe performance of WT mice and did not improve the performance in hAPP mice (Suppl. Fig. 5B–F). Thus, in aging mice with chronic plaque pathology, istradefylline enhances spatial memory primarily at low doses. Istradefylline at doses of 4, 10 and 15 mg/kg/day also improved learning of the cued navigation task in hAPP mice (Suppl. Fig. 6), possibly due to improvements in striatum-dependent navigation to the visible platform. Reference: Neurobiol Dis. 2018 Feb;110:29-36. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29100987/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 6.0 15.61

Preparing Stock Solutions

The following data is based on the product molecular weight 384.43 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:
In vitro protocol: 1. Saki M, Yamada K, Koshimura E, Sasaki K, Kanda T. In vitro pharmacological profile of the A2A receptor antagonist istradefylline. Naunyn Schmiedebergs Arch Pharmacol. 2013 Nov;386(11):963-72. doi: 10.1007/s00210-013-0897-5. Epub 2013 Jun 29. PMID: 23812646.
In vivo protocol: 1. Orr AG, Lo I, Schumacher H, Ho K, Gill M, Guo W, Kim DH, Knox A, Saito T, Saido TC, Simms J, Toddes C, Wang X, Yu GQ, Mucke L. Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol Dis. 2018 Feb;110:29-36. doi: 10.1016/j.nbd.2017.10.014. Epub 2017 Oct 31. PMID: 29100987; PMCID: PMC5747997.

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1: Deutschländer AB. Treatment with istradefylline for postural abnormalities in Parkinson's disease. Neurol Neurochir Pol. 2019;53(4):239-241. doi: 10.5603/PJNNS.2019.0038. PubMed PMID: 31469906.

2: Fujioka S, Yoshida R, Nose K, Hayashi Y, Mishima T, Fukae J, Kitano K, Kikuchi H, Tsuboi Y. A new therapeutic strategy with istradefylline for postural deformities in Parkinson's disease. Neurol Neurochir Pol. 2019;53(4):291-295. doi: 10.5603/PJNNS.a2019.0036. Epub 2019 Aug 23. PubMed PMID: 31441493.

3: Iijima M, Orimo S, Terashi H, Suzuki M, Hayashi A, Shimura H, Mitoma H, Kitagawa K, Okuma Y. Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson's disease: A single-arm, open-label, prospective, multicenter study. Expert Opin Pharmacother. 2019 Aug;20(11):1405-1411. doi: 10.1080/14656566.2019.1614167. Epub 2019 May 28. PubMed PMID: 31039621.

4: Nagayama H, Kano O, Murakami H, Ono K, Hamada M, Toda T, Sengoku R, Shimo Y, Hattori N. Effect of istradefylline on mood disorders in Parkinson's disease. J Neurol Sci. 2019 Jan 15;396:78-83. doi: 10.1016/j.jns.2018.11.005. Epub 2018 Nov 5. PubMed PMID: 30423541.

5: Takahashi M, Fujita M, Asai N, Saki M, Mori A. Safety and effectiveness of istradefylline in patients with Parkinson's disease: interim analysis of a post-marketing surveillance study in Japan. Expert Opin Pharmacother. 2018 Oct;19(15):1635-1642. doi: 10.1080/14656566.2018.1518433. Epub 2018 Oct 3. PubMed PMID: 30281377.

6: Yasuda Y. Reversible istradefylline-induced pleurothotonus in a patient with Parkinson's disease: A case report and literature review. eNeurologicalSci. 2018 Sep 10;13:5-7. doi: 10.1016/j.ensci.2018.09.001. eCollection 2018 Dec. PubMed PMID: 30258991; PubMed Central PMCID: PMC6153187.

7: Ishibashi K, Miura Y, Wagatsuma K, Toyohara J, Ishiwata K, Ishii K. Occupancy of adenosine A(2A) receptors by istradefylline in patients with Parkinson's disease using (11)C-preladenant PET. Neuropharmacology. 2018 Dec;143:106-112. doi: 10.1016/j.neuropharm.2018.09.036. Epub 2018 Sep 22. PubMed PMID: 30253174.

8: Torti M, Vacca L, Stocchi F. Istradefylline for the treatment of Parkinson's disease: is it a promising strategy? Expert Opin Pharmacother. 2018 Nov;19(16):1821-1828. doi: 10.1080/14656566.2018.1524876. Epub 2018 Oct 11. Review. PubMed PMID: 30232916.

9: Kataoka H, Sugie K. Does istradefylline really have a dystonic mechanism? J Neurol Sci. 2018 May 15;388:233-234. doi: 10.1016/j.jns.2018.03.020. Epub 2018 Mar 14. PubMed PMID: 29559176.

10: Suzuki K, Miyamoto T, Miyamoto M, Uchiyama T, Hirata K. Authors' reply to the comments of Kataoka et al. regarding "Could istradefylline be a treatment option for postural abnormalities in mid-stage Parkinson's disease?" J Neurol Sci. 2018 May 15;388:235-236. doi: 10.1016/j.jns.2018.03.019. Epub 2018 Mar 14. PubMed PMID: 29555107.

11: Nuermaimaiti M, Oyama G, Kasemsuk C, Hattori N. Istradefylline for Restless Legs Syndrome Associated with Parkinson's Disease. Tremor Other Hyperkinet Mov (N Y). 2018 Jan 8;8:521. doi: 10.7916/D86H5R1H. eCollection 2018. PubMed PMID: 29423337; PubMed Central PMCID: PMC5803507.

12: Suzuki K, Miyamoto T, Miyamoto M, Uchiyama T, Hirata K. Could istradefylline be a treatment option for postural abnormalities in mid-stage Parkinson's disease? J Neurol Sci. 2018 Feb 15;385:131-133. doi: 10.1016/j.jns.2017.12.027. Epub 2017 Dec 24. PubMed PMID: 29406892.

13: Sako W, Murakami N, Motohama K, Izumi Y, Kaji R. The effect of istradefylline for Parkinson's disease: A meta-analysis. Sci Rep. 2017 Dec 21;7(1):18018. doi: 10.1038/s41598-017-18339-1. PubMed PMID: 29269791; PubMed Central PMCID: PMC5740127.

14: Orr AG, Lo I, Schumacher H, Ho K, Gill M, Guo W, Kim DH, Knox A, Saito T, Saido TC, Simms J, Toddes C, Wang X, Yu GQ, Mucke L. Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol Dis. 2018 Feb;110:29-36. doi: 10.1016/j.nbd.2017.10.014. Epub 2017 Oct 31. PubMed PMID: 29100987; PubMed Central PMCID: PMC5747997.

15: Matsuura K, Kajikawa H, Tabei KI, Satoh M, Kida H, Nakamura N, Tomimoto H. The effectiveness of istradefylline for the treatment of gait deficits and sleepiness in patients with Parkinson's disease. Neurosci Lett. 2018 Jan 1;662:158-161. doi: 10.1016/j.neulet.2017.10.018. Epub 2017 Oct 13. PubMed PMID: 29031781.

16: Yabe I, Kitagawa M, Takahashi I, Matsushima M, Sasaki H. The Efficacy of Istradefylline for Treating Mild Wearing-Off in Parkinson Disease. Clin Neuropharmacol. 2017 Nov/Dec;40(6):261-263. doi: 10.1097/WNF.0000000000000249. PubMed PMID: 28976411.

17: Mukai M, Uchimura T, Zhang X, Greene D, Vergeire M, Cantillon M. Effects of Rifampin on the Pharmacokinetics of a Single Dose of Istradefylline in Healthy Subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201. doi: 10.1002/jcph.1003. Epub 2017 Sep 7. PubMed PMID: 28881378; PubMed Central PMCID: PMC5811788.

18: Suzuki K, Miyamoto M, Miyamoto T, Uchiyama T, Watanabe Y, Suzuki S, Kadowaki T, Fujita H, Matsubara T, Sakuramoto H, Hirata K. Istradefylline improves daytime sleepiness in patients with Parkinson's disease: An open-label, 3-month study. J Neurol Sci. 2017 Sep 15;380:230-233. doi: 10.1016/j.jns.2017.07.045. Epub 2017 Jul 29. PubMed PMID: 28870576.

19: Ko WKD, Camus SM, Li Q, Yang J, McGuire S, Pioli EY, Bezard E. An evaluation of istradefylline treatment on Parkinsonian motor and cognitive deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque models. Neuropharmacology. 2016 Nov;110(Pt A):48-58. doi: 10.1016/j.neuropharm.2016.07.012. Epub 2016 Jul 14. PubMed PMID: 27424102.

20: Kitta T, Yabe I, Takahashi I, Matsushima M, Sasaki H, Shinohara N. Clinical efficacy of istradefylline on lower urinary tract symptoms in Parkinson's disease. Int J Urol. 2016 Oct;23(10):893-894. doi: 10.1111/iju.13160. Epub 2016 Jul 8. PubMed PMID: 27388933.