Bitopertin | Paliflutine | RG 1678 | CAS#845614-11-1 | glycine reuptake inhibitor

MedKoo Cat#: 319795 | Name: Bitopertin

Description:

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

Bitopertin, also known as Paliflutine and RG-1678, is a glycine reuptake inhibitor which was under development as an adjunct to antipsychotics for the treatment of persistent negative symptoms or suboptimally-controlled positive symptoms associated with schizophrenia. Bitopertin-mediated glycine reuptake inhibition may represent a novel treatment option for schizophrenia, with the potential to address negative symptoms.

Chemical Structure

Bitopertin

CAS#845614-11-1

Theoretical Analysis

MedKoo Cat#: 319795

Name: Bitopertin

CAS#: 845614-11-1

Chemical Formula: C21H20F7N3O4S

Exact Mass: 543.1063

Molecular Weight: 543.46

Elemental Analysis: C, 46.41; H, 3.71; F, 24.47; N, 7.73; O, 11.78; S, 5.90

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,450.00	2 Weeks
2g	USD 5,950.00	2 Weeks

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Related CAS #

No Data

Synonym

RG-1678; RG1678; RG 1678; R-1678; R1678; R 1678; RO4917838; RO-4917838; RO 4917838; Bitopertin

IUPAC/Chemical Name

(S)-(4-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)(5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)phenyl)methanone

InChi Key

YUUGYIUSCYNSQR-LBPRGKRZSA-N

InChi Code

InChI=1S/C21H20F7N3O4S/c1-12(20(23,24)25)35-17-4-3-14(36(2,33)34)10-15(17)19(32)31-7-5-30(6-8-31)18-16(22)9-13(11-29-18)21(26,27)28/h3-4,9-12H,5-8H2,1-2H3/t12-/m0/s1

SMILES Code

O=C(N1CCN(C2=NC=C(C(F)(F)F)C=C2F)CC1)C3=CC(S(=O)(C)=O)=CC=C3O[C@@H](C)C(F)(F)F

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, not in water

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

Instruction

View handling instruction

Biological target:

Bitopertin (RG1678,RO-4917838) is an inhibitor of glycine transporter 1 (GlyT1), with Ki of 8.1 nM for human hGlyT1b and IC50 of 22-25 nM in Chinese hamster ovary cells.

In vitro activity:

TBD

In vivo activity:

A significant increase in Hb was also observed in Hbbth3/+ mice treated with bitopertin at lower dosages of either 3 or 10 mg/kg/d (Supplemental Figure 1A). In Hbbth3/+ mice treated with 30 mg/kg/d bitopertin, the increased Hb values were associated with an increase in RBC counts (Supplemental Figure 1B) and a slight but significant decrease in MCV (Supplemental Figure 1B) with a slightly increased MCH (Figure 1B, days 7 and 14 only). Significant decreases in absolute reticulocyte counts and in circulating erythroblasts were also found in Hbbth3/+ mice treated with bitopertin at dosages of either 30 or 10 mg/kg/d for 28 days (Figure 1B and Supplemental Figure 1C). Reference: JCI Insight. 2019 Nov 14; 4(22): e130111. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948868/

	Solvent	mg/mL	mM
Solubility
	DMSO	62.5	115.00
	DMF	30.0	55.20
	DMF:PBS (pH 7.2) (1:12)	0.3	0.46
	Ethanol	52.5	96.60

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 543.46 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. Matte A, Federti E, Winter M, Koerner A, Harmeier A, Mazer N, Tomka T, Di Paolo ML, De Falco L, Andolfo I, Beneduce E, Iolascon A, Macias-Garcia A, Chen JJ, Janin A, Lebouef C, Turrini F, Brugnara C, De Franceschi L. Bitopertin, a selective oral GLYT1 inhibitor, improves anemia in a mouse model of β-thalassemia. JCI Insight. 2019 Nov 14;4(22):e130111. doi: 10.1172/jci.insight.130111. PMID: 31593554; PMCID: PMC6948868. 2. Armbruster A, Neumann E, Kötter V, Hermanns H, Werdehausen R, Eulenburg V. The GlyT1 Inhibitor Bitopertin Ameliorates Allodynia and Hyperalgesia in Animal Models of Neuropathic and Inflammatory Pain. Front Mol Neurosci. 2018 Jan 10;10:438. doi: 10.3389/fnmol.2017.00438. PMID: 29375301; PMCID: PMC5767717.

In vitro protocol:

TBD

In vivo protocol:

1: Deiana S, Hauber W, Munster A, Sommer S, Ferger B, Marti A, Schmid B, Dorner- Ciossek C, Rosenbrock H. Pro-cognitive effects of the GlyT1 inhibitor Bitopertin in rodents. Eur J Pharmacol. 2022 Nov 15;935:175306. doi: 10.1016/j.ejphar.2022.175306. Epub 2022 Sep 30. PMID: 36183855. 2: Goff DC. Bitopertin: the good news and bad news. JAMA Psychiatry. 2014 Jun;71(6):621-2. doi: 10.1001/jamapsychiatry.2014.257. PMID: 24696065. 3: Matte A, Federti E, Winter M, Koerner A, Harmeier A, Mazer N, Tomka T, Di Paolo ML, De Falco L, Andolfo I, Beneduce E, Iolascon A, Macias-Garcia A, Chen JJ, Janin A, Lebouef C, Turrini F, Brugnara C, De Franceschi L. Bitopertin, a selective oral GLYT1 inhibitor, improves anemia in a mouse model of β-thalassemia. JCI Insight. 2019 Nov 14;4(22):e130111. doi: 10.1172/jci.insight.130111. PMID: 31593554; PMCID: PMC6948868. 4: Javitt DC. Bitopertin in schizophrenia: glass half full? Lancet Psychiatry. 2016 Dec;3(12):1092-1093. doi: 10.1016/S2215-0366(16)30354-6. Epub 2016 Nov 2. PMID: 27816569. 5: Kantrowitz JT, Nolan KA, Epstein ML, Lehrfeld N, Shope C, Petkova E, Javitt DC. Neurophysiological Effects of Bitopertin in Schizophrenia. J Clin Psychopharmacol. 2017 Aug;37(4):447-451. doi: 10.1097/JCP.0000000000000722. PMID: 28590364; PMCID: PMC5492956. 6: Frouni I, Bédard D, Bourgeois-Cayer É, Hamadjida A, Gaudette F, Beaudry F, Huot P. Pharmacokinetic profile of bitopertin, a selective GlyT1 inhibitor, in the rat. Naunyn Schmiedebergs Arch Pharmacol. 2023 May;396(5):1053-1060. doi: 10.1007/s00210-022-02378-1. Epub 2023 Jan 12. PMID: 36633618. 7: Bugarski-Kirola D, Blaettler T, Arango C, Fleischhacker WW, Garibaldi G, Wang A, Dixon M, Bressan RA, Nasrallah H, Lawrie S, Napieralski J, Ochi-Lohmann T, Reid C, Marder SR. Bitopertin in Negative Symptoms of Schizophrenia-Results From the Phase III FlashLyte and DayLyte Studies. Biol Psychiatry. 2017 Jul 1;82(1):8-16. doi: 10.1016/j.biopsych.2016.11.014. Epub 2016 Dec 15. PMID: 28117049. 8: Frouni I, Kang W, Bédard D, Belliveau S, Kwan C, Hadj-Youssef S, Bourgeois- Cayer É, Ohlund L, Sleno L, Hamadjida A, Huot P. Effect of glycine transporter 1 inhibition with bitopertin on parkinsonism and L-DOPA induced dyskinesia in the 6-OHDA-lesioned rat. Eur J Pharmacol. 2022 Aug 15;929:175090. doi: 10.1016/j.ejphar.2022.175090. Epub 2022 Jun 30. PMID: 35780824. 9: Armbruster A, Neumann E, Kötter V, Hermanns H, Werdehausen R, Eulenburg V. The GlyT1 Inhibitor Bitopertin Ameliorates Allodynia and Hyperalgesia in Animal Models of Neuropathic and Inflammatory Pain. Front Mol Neurosci. 2018 Jan 10;10:438. doi: 10.3389/fnmol.2017.00438. PMID: 29375301; PMCID: PMC5767717. 10: Hofmann C, Banken L, Hahn M, Swearingen D, Nagel S, Martin-Facklam M. Evaluation of the effects of bitopertin (RG1678) on cardiac repolarization: a thorough corrected QT study in healthy male volunteers. Clin Ther. 2012 Oct;34(10):2061-71. doi: 10.1016/j.clinthera.2012.08.010. Epub 2012 Sep 12. PMID: 22980315. 11: Hofmann C, Pizzagalli F, Boetsch C, Alberati D, Ereshefsky L, Jhee S, Patat A, Boutouyrie-Dumont B, Martin-Facklam M. Effects of the glycine reuptake inhibitors bitopertin and RG7118 on glycine in cerebrospinal fluid: results of two proofs of mechanism studies in healthy volunteers. Psychopharmacology (Berl). 2016 Jul;233(13):2429-39. doi: 10.1007/s00213-016-4317-7. Epub 2016 May 14. PMID: 27178435. 12: Umbricht D, Alberati D, Martin-Facklam M, Borroni E, Youssef EA, Ostland M, Wallace TL, Knoflach F, Dorflinger E, Wettstein JG, Bausch A, Garibaldi G, Santarelli L. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study. JAMA Psychiatry. 2014 Jun;71(6):637-46. doi: 10.1001/jamapsychiatry.2014.163. PMID: 24696094. 13: Bugarski-Kirola D, Wang A, Abi-Saab D, Blättler T. A phase II/III trial of bitopertin monotherapy compared with placebo in patients with an acute exacerbation of schizophrenia - results from the CandleLyte study. Eur Neuropsychopharmacol. 2014 Jul;24(7):1024-36. doi: 10.1016/j.euroneuro.2014.03.007. Epub 2014 Mar 29. PMID: 24735806. 14: Martin-Facklam M, Pizzagalli F, Zhou Y, Ostrowitzki S, Raymont V, Brašić JR, Parkar N, Umbricht D, Dannals RF, Goldwater R, Wong DF. Glycine transporter type 1 occupancy by bitopertin: a positron emission tomography study in healthy volunteers. Neuropsychopharmacology. 2013 Feb;38(3):504-12. doi: 10.1038/npp.2012.212. Epub 2012 Nov 7. PMID: 23132267; PMCID: PMC3547202. 15: Hirayasu Y, Sato SI, Shuto N, Nakano M, Higuchi T. Efficacy and Safety of Bitopertin in Patients with Schizophrenia and Predominant Negative Symptoms: Subgroup Analysis of Japanese Patients from the Global Randomized Phase 2 Trial. Psychiatry Investig. 2017 Jan;14(1):63-73. doi: 10.4306/pi.2017.14.1.63. Epub 2016 Dec 29. PMID: 28096877; PMCID: PMC5240458. 16: Taher AT, Viprakasit V, Cappellini MD, Kraus D, Cech P, Volz D, Winter E, Nave S, Dukart J, Khwaja O, Koerner A, Hermosilla R, Brugnara C. Haematological effects of oral administration of bitopertin, a glycine transport inhibitor, in patients with non-transfusion-dependent β-thalassaemia. Br J Haematol. 2021 Jul;194(2):474-477. doi: 10.1111/bjh.17479. Epub 2021 Apr 30. PMID: 33931857. 17: Pinard E, Borroni E, Koerner A, Umbricht D, Alberati D. Glycine Transporter Type I (GlyT1) Inhibitor, Bitopertin: A Journey from Lab to Patient. Chimia (Aarau). 2018 Aug 22;72(7):477-484. doi: 10.2533/chimia.2018.477. PMID: 30158010. 18: Hirayasu Y, Sato S, Takahashi H, Iida S, Shuto N, Yoshida S, Funatogawa T, Yamada T, Higuchi T. A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia. BMC Psychiatry. 2016 Mar 15;16:66. doi: 10.1186/s12888-016-0778-9. PMID: 26980460; PMCID: PMC4791769. 19: Boetsch C, Parrott N, Fowler S, Poirier A, Hainzl D, Banken L, Martin- Facklam M, Hofmann C. Effects of Cytochrome P450 3A4 Inhibitors-Ketoconazole and Erythromycin-on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions. Clin Pharmacokinet. 2016 Feb;55(2):237-47. doi: 10.1007/s40262-015-0312-0. PMID: 26341813. 20: Bugarski-Kirola D, Iwata N, Sameljak S, Reid C, Blaettler T, Millar L, Marques TR, Garibaldi G, Kapur S. Efficacy and safety of adjunctive bitopertin versus placebo in patients with suboptimally controlled symptoms of schizophrenia treated with antipsychotics: results from three phase 3, randomised, double-blind, parallel-group, placebo-controlled, multicentre studies in the SearchLyte clinical trial programme. Lancet Psychiatry. 2016 Dec;3(12):1115-1128. doi: 10.1016/S2215-0366(16)30344-3. Epub 2016 Nov 2. PMID: 27816567.