SH-BC-893 |enhance siRNAs and ASOs|DC Chemicals

Cas No.:	1841409-92-4
Chemical Name:	Chembl4440140
Synonyms:	Chembl4440140
SMILES:	Cl.OC[C@H]1[C@H](C2C=CC(=CC=2)CCCCCCCC)CCN1
Formula:	C₁₉H₃₂ClNO
M.Wt:	325.916484832764
Purity:	>97%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics-February 2023 Nucleic Acids Research DOI:10.1093/nar/gkad023

Description:

SH-BC-893 is a water-soluble, orally bioavailable synthetic sphingolipid that triggers nutrient transporter internalization and also blocks lysosome-dependent nutrient generation pathways in cancer cells, activates protein phosphatase 2A (PP2A), leading to mislocalization of the lipid kinase PIKfyve; selectively kills cells expressing an activated form of the anabolic oncogene Ras in vitro and in vivo.SH-BC-893, increases the activity of antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) up to 200-fold in vitro without permeabilizing endosomes. SH-BC-893 treatment trapped endocytosed oligonucleotides within extra-lysosomal compartments thought to be more permeable due to frequent membrane fission and fusion events. Simultaneous disruption of ARF6-dependent endocytic recycling and PIKfyve-dependent lysosomal fusion was necessary and sufficient for SH-BC-893 to increase non-lysosomal oligonucleotide levels and enhance their activity. In mice, oral administration of SH-BC-893 increased ASO potency in the liver by 15-fold without toxicity. More importantly, SH-BC-893 enabled target RNA knockdown in the CNS and lungs of mice treated subcutaneously with cholesterol-functionalized duplexed oligonucleotides or unmodified ASOs, respectively. Together, these results establish the feasibility of using a small molecule that disrupts endolysosomal trafficking to improve the activity of oligonucleotides in extrahepatic tissues.

References:

Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics-February 2023 Nucleic Acids Research DOI:10.1093/nar/gkad023

MSDS

COA

LOT NO.	DOWNLOAD

2018-0101
2018-0101

Cat. No.	Product name	Field of application
DC33635	DODAP	DODAP, also known as 1,2-Dioleoyl-3-dimethylammonium-propane, is a cationic lipid. It has been used as a component in liposomes that can be used to encapsulate siRNA, immunostimulatory oligodeoxynucleotides, antisense oligonucleotides, or chemotherapeutic agents for in vitro and in vivo delivery.
DC46965	Tri-GalNAc-COOH	tri-GalNAc-COOH is an asialoglycoprotein receptor (ASGPR) ligand that can be used for LYsosome TArgeting Chimera (LYTAC) research.
DC37120	Triacetin	Triacetin, the triglyceride 1,2,3-triacetoxypropane is more generally known as triacetin and glycerin triacetate. It is the triester of glycerol and acetylating agents, such as acetic acid and acetic anhydride. It is an antifungal agent.
DC34214	Tricaprilin	Tricaprilin, also known as Glyceryl trioctanoate, is a triglyceride drug candidate.
DC33460	Calcium D-saccharate tetrahydrate	Calcium saccharate is an oxidized non-cyclic hexose sugar. It may inhibit carcinogenesis and proliferation of cancer cells.
DC12399	SH-BC-893	SH-BC-893 is a water-soluble, orally bioavailable synthetic sphingolipid that triggers nutrient transporter internalization and also blocks lysosome-dependent nutrient generation pathways in cancer cells, activates protein phosphatase 2A (PP2A), leading to mislocalization of the lipid kinase PIKfyve; selectively kills cells expressing an activated form of the anabolic oncogene Ras in vitro and in vivo.SH-BC-893, increases the activity of antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) up to 200-fold in vitro without permeabilizing endosomes. SH-BC-893 treatment trapped endocytosed oligonucleotides within extra-lysosomal compartments thought to be more permeable due to frequent membrane fission and fusion events. Simultaneous disruption of ARF6-dependent endocytic recycling and PIKfyve-dependent lysosomal fusion was necessary and sufficient for SH-BC-893 to increase non-lysosomal oligonucleotide levels and enhance their activity. In mice, oral administration of SH-BC-893 increased ASO potency in the liver by 15-fold without toxicity. More importantly, SH-BC-893 enabled target RNA knockdown in the CNS and lungs of mice treated subcutaneously with cholesterol-functionalized duplexed oligonucleotides or unmodified ASOs, respectively. Together, these results establish the feasibility of using a small molecule that disrupts endolysosomal trafficking to improve the activity of oligonucleotides in extrahepatic tissues.
DC11971	NAV-2729（Grassofermata）	NAV 2729 (NAV2729) is a chemical potentiator for mRNA-LNPs, increasing the delivery efficiencies of mRNA-LNPs in vitro and in vivo. NAV 2729 (NAV2729) is a novel, direct and selective small molecule inhibitor of small GTPase ARF6 with IC50 of 1.5 uM in nucleotide exchange assays.
DC12235	LysoPC(14:0/0:0)	LysoPC(14:0/0:0) is a lysophospholipid (LyP). It is a monoglycerophospholipid in which a phosphorylcholine moiety occupies a glycerol substitution site.
DC12296	D-(+)-Trehalose dihydrate	D-(+)-Trehalose dihydrate can be used as a food ingredient and pharmaceutical excipient.