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Chemical Structure| 1094042-01-9 Chemical Structure| 1094042-01-9

Structure of CYM5442
CAS No.: 1094042-01-9

Chemical Structure| 1094042-01-9

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CYM-5442 is a highly-selective S1P1 (Spingosine 1-Phosphate Receptor 1) agonist. CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment.

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Product Citations

Product Citations

Yang, Jingdong ; Qian, Yuanyuan ; Kim, Choon ; Birhanu, Biruk T ; Cal y Mayor-Luna, Carlos ; Ding, Derong , et al.

Abstract: Clostridioides difficile, a Gram-positive, spore-forming anaerobic bacterium, is a major healthcare threat. Its spores colonize the gut following dysbiosis caused by broad-spectrum antibiotics, remaining dormant until host’s triggers germination into vegetative cells that produce toxins, leading to diarrhea, colitis, and potentially death. Current antibiotics to treat C. difficile infection target vegetative cells but not spore germination, a pivotal step in infection development. This study unveils 1,2,4-oxadiazoles as a novel class of spore germination inhibitors and delineates the structure−activity relationship. Screening of 120 revealed compound 110 (IC50 = 14 ± 1 μM or 6.3 ± 0.4 μg/mL). Compound 110 targets mature SleC (Kd = 12 ± 1.0 μM) and CspB (Kd = 8.0 ± 1.0 μM) on spores, inhibiting their enzymatic activities, thus preventing spore germination. To our knowledge, compound 110 is the first reported spore germination inhibitor targeting SleC/CspB, offering a promising avenue for C. difficile therapies.

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Product Details of CYM5442

CAS No. :1094042-01-9
Formula : C23H27N3O4
M.W : 409.48
SMILES Code : CCOC1=CC=C(C2=NC(C3=CC=CC4=C3CCC4NCCO)=NO2)C=C1OCC
MDL No. :MFCD12912402
InChI Key :NUIKTBLZSPQGCP-UHFFFAOYSA-N
Pubchem ID :25110406

Safety of CYM5442

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of CYM5442

GPCR

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
rat sensory neurons 100 nM 4-15 min CYM-5442, a selective agonist for S1PR1, significantly enhanced the excitability of sensory neurons J Neuroinflammation. 2015 Apr 12;12:70
Human umbilical vein endothelial cells (HUVECs) 200 nM 30 min To evaluate the effect of CYM5442 on IC and C5a-activated PMN-induced HUVEC barrier function. Results showed that CYM5442 rescued the PMN-induced drop in resistance, protecting endothelial cell barrier function. Arthritis Rheumatol. 2018 Nov;70(11):1879-1889
Human umbilical vein endothelial cells (HUVECs) 0.1 μM and 1 μM 24 h To investigate the effect of CYM-5442 on CCL2 and CCL7 expression in endothelial cells. Results showed that CYM-5442 significantly downregulated the mRNA expression of CCL2 and CCL7 in HUVECs. Cell Mol Immunol. 2015 Nov;12(6):681-91

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Rip-LCMV transgenic mouse model Intraperitoneal injection 10 mg/kg Once daily for 21 days CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes (e.g., Pdcd1, Lag3, Ctla4, Tigit, and Btla), thereby limiting their killing ability. By such means, insulin production was preserved and glucose regulation maintained. Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3708-3713
C57BL/6 mice Traumatic brain injury (TBI) model Intraperitoneal injection 0.3, 1, 3 mg/kg Starting 30 minutes after surgery, for 7 consecutive days CYM-5442 significantly attenuated neurological deficits and reduced brain edema in TBI mice, and decreased vesicle transcytosis of cerebrovascular endothelial cells Fluids Barriers CNS. 2022 Jul 11;19(1):57
Rats Paclitaxel-induced neuropathic pain model Oral 3 mg/kg Daily administration for 6 days To evaluate the reversal effect of CYM5442 on paclitaxel-induced neuropathic pain, results showed CYM5442 significantly attenuated mechano-hypersensitivity J Biol Chem. 2014 Jul 25;289(30):21082-97
Mice Reverse Arthus reaction (RAR) model Intraperitoneal injection 0.5 mg/kg Every 5 hours for 24 hours To evaluate the effect of CYM5442 on lung and skin RAR. Results showed that CYM5442 significantly reduced the number of PMNs and RBCs in BAL, mitigating inflammatory responses. Arthritis Rheumatol. 2018 Nov;70(11):1879-1889
Mice (BALB/c and C57BL/6) Acute graft-versus-host disease (aGVHD) model Intraperitoneal injection 3 mg/kg Once daily from day -1 to day 3 post-transplantation To evaluate the effect of CYM-5442 on the progression of aGVHD. Results showed that CYM-5442 significantly prolonged the survival of aGVHD mice, reduced body weight loss and GVHD scores, and decreased macrophage infiltration in GVHD target organs. Cell Mol Immunol. 2015 Nov;12(6):681-91

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1 mM

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10 mM

2.44mL

0.49mL

0.24mL

12.21mL

2.44mL

1.22mL

24.42mL

4.88mL

2.44mL

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