RO5263397

RO5263397
Clinical data
Other names	RO-5263397; Ro 5263397; Ro-5263397
Drug class	Trace amine-associated receptor 1 (TAAR1) agonist
Identifiers
	IUPAC name (4S)-4-(3-fluoro-2-methylphenyl)-4,5-dihydro-1,3-oxazol-2-amine;
CAS Number	1357266-05-7;
PubChem CID	56835991;
ChemSpider	35523070;
UNII	Y2P4KD8GDR;
ChEMBL	ChEMBL3781694;
Chemical and physical data
Formula	C10H11FN2O
Molar mass	194.209 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C=CC=C1F)[C@H]2COC(=N2)N;
	InChI InChI=1S/C10H11FN2O/c1-6-7(3-2-4-8(6)11)9-5-14-10(12)13-9/h2-4,9H,5H2,1H3,(H2,12,13)/t9-/m1/s1; Key:IOHOUWIYOVWGHV-SECBINFHSA-N;

RO5263397, or RO-5263397, is a trace amine-associated receptor 1 (TAAR1) partial agonist which is used in scientific research.^[1]^[2]^[3]

Pharmacology

Pharmacodynamics

Actions

RO5263397 is a trace amine-associated receptor 1 (TAAR1) partial agonist.^[4]^[3] Its EC₅₀Tooltip half-maximal effective concentration values are 0.12 to 7.5 nM for the mouse TAAR1 (mTAAR1), 35 to 47 nM for the rat TAAR1 (rTAAR1), 251 nM at the cynomolgus monkey TAAR1, and 17 to 85 nM for the human TAAR1 (hTAAR1).^[2]^[4]^[3] Its intrinsic activity (E_max) is 59 to 64% at the mTAAR1, 69 to 76% at the rTAAR1, 85% at the cynomolgus monkey TAAR1, and 81 to 82% at the hTAAR1.^[4]^[3]

RO5263397 at TAAR1 in different species^[4]^[3]^[2]
Species	Affinity (K_i, nM)	EC₅₀Tooltip half-maximal effective concentration (nM)	E_maxTooltip maximal efficacy (%)
Mouse	0.9	0.12–7.5	59–64%
Rat	9.1	35–47	69–76%
Monkey	24	251	85%
Human	4.1	17–85	81–82%

Effects

Similarly to other TAAR1 agonists like RO5166017 and RO5256390, RO5263397 shows aversive effects in animals.^[5]^[6]

References

^ Schwartz MD, Canales JJ, Zucchi R, Espinoza S, Sukhanov I, Gainetdinov RR (June 2018). "Trace amine-associated receptor 1: a multimodal therapeutic target for neuropsychiatric diseases". Expert Opinion on Therapeutic Targets. 22 (6): 513–526. doi:10.1080/14728222.2018.1480723. hdl:11568/930006. PMID 29798691.
^ ^a ^b ^c "RO 5263397 hydrochloride Supplier". Tocris Bioscience. Retrieved 29 October 2024. RO 5263397 hydrochloride is a potent trace amine 1 (TA1) receptor agonist (EC50 values are 0.12, 35 and 17-85 nM for mouse, rat and human receptors, respectively). Increases wakefulness and reduces REM and NREM sleep duration in wild type mice. Inhibits spontaneous locomotor activity in dopamine transport (DAT) knockout mice.
^ ^a ^b ^c ^d ^e Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, et al. (May 2013). "A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight". Mol Psychiatry. 18 (5): 543–556. doi:10.1038/mp.2012.57. PMID 22641180.
^ ^a ^b ^c ^d Galley G, Beurier A, Décoret G, Goergler A, Hutter R, Mohr S, et al. (February 2016). "Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists". ACS Med Chem Lett. 7 (2): 192–197. doi:10.1021/acsmedchemlett.5b00449. PMC 4753552. PMID 26985297.
^ Shabani S, Houlton S, Ghimire B, Tonello D, Reed C, Baba H, et al. (September 2023). "Robust aversive effects of trace amine-associated receptor 1 activation in mice". Neuropsychopharmacology. 48 (10): 1446–1454. doi:10.1038/s41386-023-01578-4. PMC 10425385. PMID 37055488.
^ Liu J, Wu R, Johnson B, Zhang Y, Zhu Q, Li JX (October 2022). "Selective TAAR1 agonists induce conditioned taste aversion". Psychopharmacology. 239 (10): 3345–3353. doi:10.1007/s00213-022-06222-5. PMID 36056214.

[SchwartzCanalesZucchi2018-1] Schwartz MD, Canales JJ, Zucchi R, Espinoza S, Sukhanov I, Gainetdinov RR (June 2018). "Trace amine-associated receptor 1: a multimodal therapeutic target for neuropsychiatric diseases". Expert Opinion on Therapeutic Targets. 22 (6): 513–526. doi:10.1080/14728222.2018.1480723. hdl:11568/930006. PMID 29798691.

[Tocris-2] "RO 5263397 hydrochloride Supplier". Tocris Bioscience. Retrieved 29 October 2024. RO 5263397 hydrochloride is a potent trace amine 1 (TA1) receptor agonist (EC50 values are 0.12, 35 and 17-85 nM for mouse, rat and human receptors, respectively). Increases wakefulness and reduces REM and NREM sleep duration in wild type mice. Inhibits spontaneous locomotor activity in dopamine transport (DAT) knockout mice.

[RevelMoreauPouzet2013-3] Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, et al. (May 2013). "A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight". Mol Psychiatry. 18 (5): 543–556. doi:10.1038/mp.2012.57. PMID 22641180.

[GalleyBeurierDécoret2016-4] Galley G, Beurier A, Décoret G, Goergler A, Hutter R, Mohr S, et al. (February 2016). "Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists". ACS Med Chem Lett. 7 (2): 192–197. doi:10.1021/acsmedchemlett.5b00449. PMC 4753552. PMID 26985297.

[ShabaniHoultonGhimire2023-5] Shabani S, Houlton S, Ghimire B, Tonello D, Reed C, Baba H, et al. (September 2023). "Robust aversive effects of trace amine-associated receptor 1 activation in mice". Neuropsychopharmacology. 48 (10): 1446–1454. doi:10.1038/s41386-023-01578-4. PMC 10425385. PMID 37055488.

[LiuWuJohnson2022-6] Liu J, Wu R, Johnson B, Zhang Y, Zhu Q, Li JX (October 2022). "Selective TAAR1 agonists induce conditioned taste aversion". Psychopharmacology. 239 (10): 3345–3353. doi:10.1007/s00213-022-06222-5. PMID 36056214.

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Pharmacology

Pharmacodynamics

Actions

Effects

See also

References