MedKoo Cat#: 555325 | Name: LIT-001 TFA
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Description:

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

LIT-001 is the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism.

Chemical Structure

LIT-001 TFA
CAS#2245072-21-1 (TFA)

Theoretical Analysis

MedKoo Cat#: 555325

Name: LIT-001 TFA

CAS#: 2245072-21-1 (TFA)

Chemical Formula: C30H34F3N7O4S

Exact Mass: 0.0000

Molecular Weight: 645.70

Elemental Analysis: C, 55.80; H, 5.31; F, 8.83; N, 15.18; O, 9.91; S, 4.97

Price and Availability

Size Price Availability Quantity
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,250.00 Ready to ship
200mg USD 1,950.00 Ready to ship
500mg USD 3,850.00 Ready to ship
1g USD 6,150.00 Ready to ship
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Synonym
LIT-001; LIT 001; LIT001; LIT-001 TFA; LIT-001; LIT001; LIT 001;
IUPAC/Chemical Name
(S)-2-(Dimethylcarbamothioyl)-N-(2-methyl-4-(1-methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine-5-carbonyl)benzyl)pyrrolidine-1-carboxamide, Trifluoroacetate
InChi Key
BZHSRXWFCSEPQQ-JIDHJSLPSA-N
InChi Code
InChI=1S/C28H33N7O2S.C2HF3O2/c1-18-14-19(11-12-20(18)15-29-28(37)34-13-7-10-24(34)27(38)32(2)3)26(36)35-17-21-16-30-33(4)25(21)31-22-8-5-6-9-23(22)35;3-2(4,5)1(6)7/h5-6,8-9,11-12,14,16,24,31H,7,10,13,15,17H2,1-4H3,(H,29,37);(H,6,7)/t24-;/m0./s1
SMILES Code
O=C(N1[C@H](C(N(C)C)=S)CCC1)NCC2=CC=C(C(N3C4=CC=CC=C4NC(N(C)N=C5)=C5C3)=O)C=C2C.O=C(O)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
Shelf Life
>3 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
Biological target:
LIT-001 is the first nonpeptide oxytocin receptor (OT-R) agonist (EC50=55 nM; Ki=226 nM).
In vitro activity:
LIT-001 (compound 57) was further studied its pharmacological profile by assessing its effects on calcium release and β-arrestin2 recruitment in HEK293FT cell lines transiently expressing human OT, V1a, V1b, or V2 receptors with either aequorin sensor or β-arrestin2 for calcium or BRET1 recruitment assays, respectively. This activity was compared to those of several reference molecules: oxytocin and carbetocin as full and biased peptide agonists, respectively, and WAY-267464 as nonpeptide partial agonist (Figure 1 and Table 5). Regarding calcium release (Figure 1A and Table 5), oxytocin was the most potent agonist on OT-R; carbetocin, WAY-267464, and compound 57 had similar potencies (EC50 = 25 nM), with compound 57 showing the best maximal effect (Emax = 96%). These four compounds were compared on mouse OT-R calcium release prior to in vivo testing in mice. Oxytocin was the most potent agonist, and compound 57 showed better potency (EC50 = 18 nM) and maximal effect (Emax = 96%) than carbetocin and WAY-267464 (Supporting Information, Figure S1A and Table 5). Now focusing on β-arrestin recruitment (Figure 1B and Table 5), carbetocin retained a high potency (EC50 = 10 nM) however with a partial maximal response (Emax = 42%); WAY-267464 showed a 6-fold lower potency compared to that measured for calcium release, suggesting a potential bias in its signaling. Compound 57 retained high potency (EC50 = 62 nM) and maximal response (Emax = 77%). Thus, compound 57 was the most potent agonist behind oxytocin to recruit β-arrestin. Furthermore, the specificity of previous compounds was tested by measuring their effects on V1a, V1b, and V2 vasopressin receptor-mediated activation of calcium release and β-arrestin recruitment (Figure 1C–H and Table 5). Carbetocin poorly activated V1b-R and V2-R without effect on V1a-R-induced calcium release. It had no effect on β-arrestin recruitment mediated by V1a-R and V1b-R and a very small effect on V2-R mediated arrestin release (Emax = 8% at micromolar concentration). WAY-267464 activated partially V2-R mediated calcium release (EC50 = 2300 nM; Emax = 43%) and had no effect on AVP induced arrestin release on the three receptor subtypes. WAY-267464 is also known to antagonize V1a receptors. 57 was tested to see if it would similarly block the effects of vasopressin on V1a and V1b receptors. It was found that compound 57 poorly antagonized vasopressin induced calcium release on V1a-R (IC50 = 5900 nM) and was devoid of effect on V1b-R (Supporting Information, Figure S1B,C). However, compound 57 significantly activated V2 receptors as measured on both pathways. Finally, the effects of the Pfizer OT-R antagonist PF 3274167(72) on the activation of OT and V2 receptors were tested by compound 57. PF3274167 totally suppressed and partially reduced the effects of 57 on OT-R and V2-R, respectively (Table 5; Supporting Information, Figure S1D,E). In conclusion, compound 57 acts as a nonbiased agonist on OT-R with the most potent and specific effects among tested synthetic compounds. Reference: J Med Chem. 2018 Oct 11;61(19):8670-8692. https://doi.org/10.1021/acs.jmedchem.8b00697
In vivo activity:
An acute intraperitoneal injection of vehicle or 57 (at 10 or 20 mg/kg) to Oprm1+/+ or Oprm1–/– unfamiliar (non cagemates, same age, same sex, and same treatment) were administered on mice before introducing them by pairs in an open-field for 10 min testing. Behavioral parameters were scored on video recordings to assess the quality of social interactions in these animals, namely the number of nose contacts (NCs), the time spent in NC, the mean duration of NCs, the number of following episodes, and the number of grooming episodes occurring after a social contact, an index of social avoidance. At the dose of 10 mg/kg (Figure 2), 57 restored the number of NCs (genotype effect, F1,42 = 54.2, p < 0.0001; dose effect, F2,42 = 9.6, p < 0.001; genotype × dose interaction, F2,42 = 16.8, p < 0.0001) and time spent in NC (genotype, F1,42 = 45.6, p < 0.0001; dose, F2,42 = 19.9, p < 0.0001; genotype × dose: F2,42 = 17.4, p < 0.0001), the mean duration of NC (genotype, F1,42 = 15.1, p < 0.001; dose, F2,42 = 19.5, p < 0.0001; genotype × dose, F2,42 = 19.8, p < 0.0001) and the number of following episodes (genotype, F1,42 = 38.9, p < 0.001; dose, F2,42 = 24.4, p < 0.0001; genotype × dose, F2,42 = 4.2, p < 0.05) measured in Oprm1–/– mice to similar levels as measured in wild-type controls. Moreover, at this dose, 57 also suppressed grooming episodes occurring after a social contact in mutants (genotype, F1,42 = 8.5, p < 0.01; dose, F2,42 = 11.3, p < 0.001; genotype × dose, F2,42 = 21.4, p < 0.0001). The OT-R agonist had no effect in Oprm1+/+ mice at this dose, except that it increased the number of following episodes. At the dose of 20 mg/kg, compound 57 demonstrated less significant beneficial effects on social parameters measured in mutant animals and started to show some detrimental effects on these parameters in wild-type controls (Figure 2A–E). Such effects may have resulted either from excessive OT-R activation or from recruitment/blockade of V1a or V1b vasopressin receptors at high doses, peripherally or centrally. Reference: J Med Chem. 2018 Oct 11;61(19):8670-8692. https://doi.org/10.1021/acs.jmedchem.8b00697
Solvent mg/mL mM comments
Solubility
DMSO 250.0 387.18
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 645.70 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. Frantz MC, Pellissier LP, Pflimlin E, Loison S, Gandía J, Marsol C, Durroux T, Mouillac B, Becker JAJ, Le Merrer J, Valencia C, Villa P, Bonnet D, Hibert M. LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism. J Med Chem. 2018 Oct 11;61(19):8670-8692. doi: 10.1021/acs.jmedchem.8b00697. Epub 2018 Sep 24. PMID: 30199637.
In vivo protocol:
1. Frantz MC, Pellissier LP, Pflimlin E, Loison S, Gandía J, Marsol C, Durroux T, Mouillac B, Becker JAJ, Le Merrer J, Valencia C, Villa P, Bonnet D, Hibert M. LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism. J Med Chem. 2018 Oct 11;61(19):8670-8692. doi: 10.1021/acs.jmedchem.8b00697. Epub 2018 Sep 24. PMID: 30199637.
1: Frantz MC, Pellissier L, Pflimlin E, Loison S, Gandia J, Marsol C, Durroux T, Mouillac B, Becker J, Le Merrer J, Valencia C, Villa P, Bonnet D, Hibert M. LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism. J Med Chem. 2018 Sep 10. doi: 10.1021/acs.jmedchem.8b00697. [Epub ahead of print] PubMed PMID: 30199637.