[CAS NO. 155270-99-8] Istradefylline
PRODUCTS SPECIFICATIONS [155270-99-8]
DESCRIPTION [155270-99-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 384.43 |
| Molecular Formula | C20H24N4O4 |
| SMILES | O=C1C2=C(N=C(/C=C/C3=CC(OC)=C(OC)C=C3)N2C)N(CC)C(N1CC)=O |
6 Publications Citing Use of MCE
Summary
Istradefylline is a very potent, selective and orally active adenosine A2A receptor antagonist with K i of 2.2 nM in experimental models of Parkinson's disease.
IC50 & Target
Ki: 2.2 nM (adenosine A2A receptor)
In Vitro
Istradefylline has 70-fold greater affinity for the A2AR than the A1 receptor with K i of 2.2 nM versus 150 nM [1] . Istradefylline causes concentration-dependent abolition of bFGF induction of astrogliosis in primary rat striatal astrocytes [4] . Istradefylline binds to A1 receptor, A2A receptor, and A3 receptor in human with K i s of >287 nM, 9.12 nM, and >681 nM, respectively, 50.9 nM and 1.57 nM for A1 receptor and A2A receptor in rat, 105.02 nM and 1.87 nM for A1 receptor and A2A receptor in mouse, respectively [5] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Istradefylline (3.3 mg/kg, i.p.) treatment before a single dose of MPTP attenuates the partial dopamine and DOPAC depletions measured in striata 1 week later [1] . Istradefylline reverses CGS21680-induced and reserpine-induced catalepsy with an ED 50 of 0.05 mg/kg and 0.26 mg/kg, respectively. Istradefylline is over 10 times as potent in these models compared to other adenosine antagonists and dopamine agonist drugs. Istradefylline combined with L-dopa cuases potent effects on haloperidol-induced and reserpine-induced catalepsy [2] . Istradefylline (10 mg/kg, p.o.) results an increase in locomotor activity to approximately twice that of control and improves motor disability in MPTP-treated common marmosets. Istradefylline (10 mg/kg, p.o.) in combination with SKF80723, quinpirole, or L-DOPA produces a significant additive effect on locomotor activity and improvement of motor disability but not dysK i nesia [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02609477 | Kyowa Hakko Kirin Pharma, Inc.|Kyowa Kirin Co., Ltd.|Kyowa Kirin, Inc. |
Drug Abuse
|
January 2016 | Phase 1 |
| NCT00199368 | Kyowa Kirin, Inc.|Kyowa Hakko Kirin UK, Ltd. |
Parkinson´s Disease
|
October 2004 | Phase 3 |
| NCT00199381 | Kyowa Kirin, Inc. |
Parkinson´s Disease
|
October 2005 | Phase 3 |
| NCT05377424 | University of Florida|ALS Association |
ALS
|
June 21, 2022 | Phase 1|Phase 2 |
| NCT02610231 | Kyowa Hakko Kirin Pharma, Inc.|Kyowa Kirin Co., Ltd.|Kyowa Kirin, Inc. |
Idiopathic Parkinson´s Disease
|
December 2015 | Phase 3 |
| NCT05182151 | Medical University of South Carolina|Kyowa Kirin, Inc. |
Apathy|Parkinson Disease
|
July 29, 2022 | |
| NCT00203957 | University of Chicago |
Parkinson´s Disease
|
March 2005 | Phase 3 |
| NCT05217498 | Randy Trumbower, PT, PhD|Spaulding Rehabilitation Hospital |
Spinal Cord Injuries|Myelopathy
|
September 1, 2022 | Phase 1|Phase 2 |
| NCT00199446 | Kyowa Kirin, Inc. |
Sleep Disorder|Restless Legs Syndrome
|
July 2005 | Phase 2 |
| NCT02256033 | Kyowa Hakko Kirin Pharma, Inc.|Kyowa Kirin, Inc. |
Hepatic Impairment
|
August 2014 | Phase 1 |
| NCT00199394 | Kyowa Hakko Kirin UK, Ltd.|Kyowa Kirin, Inc. |
Parkinson´s Disease
|
November 2004 | Phase 3 |
| NCT00957203 | Kyowa Kirin Co., Ltd. |
Parkinson´s Disease
|
October 2009 | Phase 3 |
| NCT00199420 | Kyowa Kirin, Inc. |
Parkinson´s Disease
|
July 2004 | Phase 3 |
| NCT00006337 | National Institute of Neurological Disorders and Stroke (NINDS)|National Institutes of Health Clinical Center (CC) |
Parkinson´s Disease
|
October 2000 | Phase 2 |
| NCT00955045 | Kyowa Kirin, Inc. |
Parkinson´s Disease
|
August 2002 | Phase 2|Phase 3 |
| NCT02174250 | Kyowa Hakko Kirin Pharma, Inc.|Kyowa Kirin, Inc. |
Parkinson´s Disease
|
June 2014 | Phase 1 |
| NCT00199433 | Kyowa Kirin, Inc. |
Parkinson´s Disease|Movement Disorder Syndrome
|
May 2005 | Phase 2 |
| NCT01968031 | Kyowa Hakko Kirin Pharma, Inc.|Kyowa Kirin Co., Ltd.|Kyowa Kirin, Inc. |
Idiopathic Parkinson´s Disease
|
October 2013 | Phase 3 |
| NCT05333549 | Virginia Commonwealth University|Kyowa Kirin, Inc. |
Parkinson Disease|Cognitive Impairment
|
July 18, 2022 | Phase 2 |
| NCT00250393 | Kyowa Kirin Co., Ltd. |
Parkinson´s Disease
|
November 2005 | Phase 2 |
| NCT00455507 | Kyowa Kirin Co., Ltd. |
Parkinson´s Disease
|
March 2007 | Phase 2 |
| NCT00199355 | Kyowa Kirin Co., Ltd. |
Parkinson´s Disease
|
April 2005 | Phase 2 |
| NCT00955526 | Kyowa Kirin Co., Ltd. |
Parkinson´s Disease
|
July 2009 | Phase 3 |
| NCT00456586 | Kyowa Kirin, Inc. |
Parkinson´s Disease
|
April 2002 | Phase 2 |
| NCT00199407 | Kyowa Kirin, Inc. |
Parkinson´s Disease
|
June 2004 | Phase 3 |
| NCT00456794 | Kyowa Kirin, Inc. |
Parkinson´s Disease
|
March 2002 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 25.33 mg/mL ( 65.89 mM ; Need ultrasonic and warming)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6013 mL | 13.0063 mL | 26.0125 mL |
| 5 mM | 0.5203 mL | 2.6013 mL | 5.2025 mL |
| 10 mM | 0.2601 mL | 1.3006 mL | 2.6013 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (5.41 mM); Clear solution
References
- [1] Chen JF, et al. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease. J Neurosci. 2001 May 15;21(10):RC143.
- [2] Shiozaki S, et al. Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology (Berl). 1999 Nov;147(1):90-5.
- [3] Kanda T, et al. Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys. Exp Neurol. 2000 Apr;162(2):321-7.
- [4] Brambilla R, et al. Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes. Glia. 2003 Aug;43(2):190-4.
- [5] Mihara T, et al. Pharmacological characterization of a novel, potent adenosine A1 and A2A receptor dual antagonist, 5-[5-amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854), in models of Parkinson's disease and cognition. J Pharm
Synonyms