PeptideDB

Sibofimloc 1616113-45-1

Sibofimloc 1616113-45-1

CAS No.: 1616113-45-1

Sibofimloc (Antibiotic-202) is an oral, gut-restricted, first-in-class FimH adhesion inhibitor that was taken from Compo
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This product is for research use only, not for human use. We do not sell to patients.

Sibofimloc (Antibiotic-202) is an oral, gut-restricted, first-in-class FimH adhesion inhibitor that was taken from Compound Example 202 of patent WO2014100158A1. There is anti-bacterial infectious activity in sibofimloc. The purpose of sibofimloc is to treat inflammatory bowel disease (IBD).

Physicochemical Properties


Molecular Formula C35H39NO11
Molecular Weight 649.693
Exact Mass 649.252
Elemental Analysis C, 64.71; H, 6.05; N, 2.16; O, 27.09
CAS # 1616113-45-1
Related CAS # 1616113-45-1;
PubChem CID 76684239
Appearance Typically exists as solid at room temperature
Density 1.6±0.1 g/cm3
Boiling Point 993.7±65.0 °C at 760 mmHg
Flash Point 554.7±34.3 °C
Vapour Pressure 0.0±0.3 mmHg at 25°C
Index of Refraction 1.735
LogP 4.01
Hydrogen Bond Donor Count 8
Hydrogen Bond Acceptor Count 11
Rotatable Bond Count 4
Heavy Atom Count 47
Complexity 1190
Defined Atom Stereocenter Count 10
SMILES

C(=O)(N1CCC2(CC1)C1=C(C=CC(C#C[C@@H]3[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O3)=C1)C1=C2C=C(C#C[C@@H]2[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)C=C1)C

InChi Key SFHMWDMKUYVSQJ-VECBPBMLSA-N
InChi Code

InChI=1S/C35H39NO11/c1-18(39)36-12-10-35(11-13-36)23-14-19(4-8-25-29(40)33(44)31(42)27(16-37)46-25)2-6-21(23)22-7-3-20(15-24(22)35)5-9-26-30(41)34(45)32(43)28(17-38)47-26/h2-3,6-7,14-15,25-34,37-38,40-45H,10-13,16-17H2,1H3/t25-,26-,27-,28-,29-,30-,31-,32-,33-,34-/m1/s1
Chemical Name

1-[2,7-bis[2-[(2R,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]ethynyl]spiro[fluorene-9,4′-piperidine]-1′-yl]ethanone
Synonyms

Sibofimloc; Antibiotic-202; 1616113-45-1; VRT-1353385
HS Tariff Code 2934.99.9001
Storage

Powder-20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity


Targets FimH adhesion
ln Vitro FimH is a TLR4 receptor that is expressed by Enterobacteriaceae, including E. Coli, in CD-positive hosts. The prevention of a sub-mucosal infection that could cause mucosal inflammation and disruption of the epithelial barrier could be achieved by inhibiting FimH adhesion and, as a result, the intracellular replication of adherent-invasive E. coli in epithelial cells.
References

[1]. Preparation of mannose derivatives via coupling and click cycloaddition reactions for treating bacterial infections. From PCT Int. Appl. (2014), WO 2014100158 A1 20140626.

[2]. P568 An open-label, multicenter, phase ib, pharmacokinetic (pk) and safety study of a fimh blocker, Sibofimloc (TAK-018/EB8018), in patients with Crohn’s disease (CD), Journal of Crohn's and Colitis, Volume 14, Issue Supplement_1, January 2020: S479–S480.

Additional Infomation Sibofimloc is under investigation in clinical trial NCT03943446 (TAK-018 for Prevention of the Recurrence of Postoperative Crohn's Disease (CD)).

Solubility Data


Solubility (In Vitro) DMSO : ≥ 31 mg/mL (~47.72 mM )
Solubility (In Vivo) Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300:Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)

Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.5392 mL 7.6960 mL 15.3920 mL
5 mM 0.3078 mL 1.5392 mL 3.0784 mL
10 mM 0.1539 mL 0.7696 mL 1.5392 mL
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.