Drug Information

Drug (ID: DG01836) and It's Reported Resistant Information

• Name: Lipopolysaccharide
• Synonyms: Lipopolysaccharide; Lipopolysaccharides; LPSLPS; NCGC00188939-01
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (6 diseases)
  Hepatic fibrosis/cirrhosis [ICD-11: DB93]; [1]
  Osteomyelitis/osteitis [ICD-11: FB84]; [2]
  Periodontal disease [ICD-11: DA0C]; [3]
  Rheumatoid arthritis [ICD-11: FA20]; [4]
  Sepsis [ICD-11: 1G40]; [5]
  Systemic inflammatory response syndrome [ICD-11: MG46]; [6]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Acute lung injury [ICD-11: NB32]; [7]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (4 diseases)
  Acute lung injury [ICD-11: NB32]; [8]
  Central nervous system infection [ICD-11: 1C8Y]; [9]
  Neonatal pneumonia [ICD-11: KB24]; [10]
  Ulcer [ICD-11: EH90]; [11]
• Target: .; NOUNIPROTAC; [2]
• Formula: 154
• IsoSMILES: CCCCCCCCCCCCCCCC1[C@H](OC([C@H]([C@@H]1OC(=O)CC(CCCCCCCCCCC)O)O)CO[C@H]2[C@H](C([C@@H](C(O2)CO[C@@]3(CC([C@H](C(O3)C(CO)O)O[C@H]4[C@@H](C([C@@H](C(O4)C(CO)O)OP(=O)(O)OP(=O)(O)OCCN)O[C@@H]5[C@@H](C([C@@H](C(O5)C(CO[C@@H]6[C@@H](C([C@](CO6)(C(CO)O)O)O)O)O)OP(=O)(O)O)O[C@@H]7C(C([C@@H](C(O7)CO[C@@H]8C(C([C@H](C(O8)CO)O)O)O)O)O[C@@H]9C(C([C@H](C(O9)CO)O)O)O[C@@H]1C(C([C@@H](C(O1)CO)O[C@@H]1C(C([C@H](C(O1)CO)O)OC1[C@@H](C(C([C@@H](O1)C)O[C@@H]1C(C([C@@H](C(O1)CO)O)O[C@@H]1C(C[C@H](C(O1)C)O)O)O[C@@H]1C(C([C@H](C(O1)CO)O)O)O)O)O)O)O)O[C@@H]1[C@H](C([C@@H](C(O1)CO)O)O)NC(=O)C)O)O)O)O[C@@]1(CC([C@H](C(O1)C(CO)O)O)O[C@@]1(CC([C@H](C(O1)C(CO)O)O)O)C(=O)O)C(=O)O)C(=O)O)OP(=O)(O)O)OC(=O)CC(CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)NC(=O)CC(CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)CP(=O)(O)O
• InChI: InChI=1S/C205H366N3O117P5/c1-10-16-22-28-34-40-42-43-45-50-55-61-67-73-109-130(101-326(269,270)271)292-127(147(245)164(109)302-135(235)78-106(222)70-64-58-52-46-36-30-24-18-12-3)98-283-186-138(208-132(232)79-107(71-65-59-53-47-37-31-25-19-13-4)290-133(233)74-68-62-56-49-39-33-27-21-15-6)173(303-136(236)80-108(72-66-60-54-48-38-32-26-20-14-5)291-134(234)75-69-63-57-51-44-41-35-29-23-17-11-2)172(322-327(272,273)274)129(301-186)100-286-203(199(262)263)84-119(318-205(201(266)267)83-118(144(242)166(320-205)114(227)86-210)317-204(200(264)265)82-112(225)139(237)165(319-204)113(226)85-209)171(169(321-203)116(229)88-212)308-194-161(259)178(182(167(305-194)115(228)87-211)324-330(280,281)325-329(278,279)287-77-76-206)313-195-160(258)177(181(323-328(275,276)277)168(306-195)117(230)97-282-188-162(260)184(261)202(268,102-285-188)131(231)96-220)312-193-159(257)175(148(246)128(300-193)99-284-189-154(252)150(248)141(239)121(90-214)294-189)310-196-179(152(250)143(241)123(92-216)297-196)315-197-180(314-187-137(207-105(9)221)149(247)140(238)120(89-213)293-187)157(255)170(126(95-219)299-197)307-192-158(256)174(145(243)124(93-217)296-192)309-190-156(254)153(251)163(104(8)289-190)304-198-183(316-191-155(253)151(249)142(240)122(91-215)295-191)176(146(244)125(94-218)298-198)311-185-111(224)81-110(223)103(7)288-185/h103-104,106-131,137-198,209-220,222-231,237-261,268H,10-102,206H2,1-9H3,(H,207,221)(H,208,232)(H,262,263)(H,264,265)(H,266,267)(H,278,279)(H,280,281)(H2,269,270,271)(H2,272,273,274)(H2,275,276,277)/t103 ,104-,106 ,107 ,108 ,109 ,110+,111 ,112 ,113 ,114 ,115 ,116 ,117 ,118 ,119 ,120 ,121 ,122 ,123 ,124 ,125 ,126 ,127 ,128 ,129 ,130+,131 ,137-,138-,139+,140+,141-,142-,143-,144+,145-,146+,147+,148+,149 ,150 ,151 ,152 ,153 ,154 ,155 ,156+,157 ,158 ,159 ,160+,161+,162+,163 ,164+,165 ,166 ,167 ,168 ,169 ,170+,171+,172+,173 ,174 ,175 ,176 ,177 ,178 ,179 ,180 ,181+,182+,183 ,184 ,185+,186+,187+,188-,189-,190 ,191+,192+,193+,194-,195+,196+,197+,198+,202-,203+,204+,205+/m0/s1
• InChIKey: YPXVSQSYDIMPDZ-AUUHBOKRSA-N
• PubChem CID: 11970143

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Central nervous system infection [ICD-11: 1C8Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: prostaglandin-endoperoxide synthase 2, opposite strand 2 (Ptgs2os2) [9]

• Molecule Alteration: Down-regulation; Expression
• Resistant Disease: Central nervous system infection [ICD-11: 1C8Y.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Mouse primary microglia cells; N.A.; Homo sapiens (Human); CVCL_1110
• In Vitro Model: BV-2 cells; Brain; Mus musculus (Mouse); CVCL_0182
• In Vivo Model: C57BL/6N mouse model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Intranasal delivery of EV-loaded small RNA could be developed as therapeutics for treatment of a multitude of CNS disorders.

Sepsis [ICD-11: 1G40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [12]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay; qRT-PCR; Western bloting analysis; Luciferase assay; RNA pull down assay
• Mechanism Description: Silence of NEAT1 suppressed LPS-induced inflammatory response of macrophages by mediating miR-17-5p and TLR4, indicating that NEAT1 might be a promising target for sepsis treatment.

Key Molecule: Maternally expressed 3 (MEG3) [4]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: AC16 cells; Heart; Homo sapiens (Human); CVCL_4U18
• In Vitro Model: Human primary renal mixed epithelial cells (ATCC? PCS-400-012?); N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Overexpression assay; Knockdown assay
• Experiment for Drug Resistance: Flow cytometry assay assay
• Mechanism Description: LncRNA MEG3 overexpression may be involved in sepsis, and the downregulation of LncRNA MEG3 may serve as a potential therapeutic target for sepsis.

Key Molecule: H19, imprinted maternally expressed transcript (H19) [5]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: UL-1 cells; Ascites; Canis lupus familiaris (Dog); CVCL_L421
• In Vivo Model: Male BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Overexpression assay
• Mechanism Description: LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis.

ICD-13: Digestive system diseases

Periodontal disease [ICD-11: DA0C]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [3]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Periodontitis [ICD-11: DA0C.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Primary human gingival fibroblast cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR; Luciferase assay; RIP experiments assay; Mimic; Overexpression assay; Enzyme-linked immunosorbent assay; Western bloting analysis
• Mechanism Description: LncRNA MALAT1 regulates inflammatory cytokine production in lipopolysaccharide-stimulated human gingival fibroblasts through sponging miR-20a and activating TLR4 pathway.

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Taurine up-regulated 1 (TUG1) [1]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Hepatic cirrhosis [ICD-11: DB93.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: LSECs; Liver; Homo sapiens (Human); CVCL_QY34
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay; qRT-PCR; Western bloting analysis; Co-immunofluorescence staining; Immunohistochemical assay; RNA-seq; Luciferase assay; FISH assay; RIP experiments assay; ELISA assay
• Experiment for Drug Resistance: WST assay; Flow cytometry assay; Transwell assay
• Mechanism Description: TUG1 promotes LPS-induced autophagy and EndMT of LSECs by functioning as an endogenous sponge for miR-142-3p and promoting the expression of A TG5. LPS and miR-142-3p are potential diagnostic and therapeutic targets in cirrhosis.

ICD-14: Skin diseases

Ulcer [ICD-11: EH90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: ENSG00000247844 (CCAT1) [11]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Pressure ulceration [ICD-11: EH90]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• Experiment for Molecule Alteration: Overexpression assay; Knockdown assay; Western bloting analysis; ELISA assay; qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: The anti-inflammatory activity of sinomenine might be mediated by CCAT1 down-regulation.

ICD-15: Musculoskeletal/connective-tissue diseases

Rheumatoid arthritis [ICD-11: FA20]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Maternally expressed 3 (MEG3) [4]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Regulation; hsa04150
• In Vitro Model: Rat chondrocyte isolates; N.A.; .; N.A.
• In Vivo Model: Male SD rat model; Rattus norvegicus
• Experiment for Molecule Alteration: Overexpression assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA MEG3 inhibits rheumatoid arthritis through miR-141 and inactivation of AKT/mTOR signalling pathway.

Osteomyelitis/osteitis [ICD-11: FB84]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: MELTF antisense RNA 1 (MELTF-AS1) [2]

• Molecule Alteration: Up-regulation; Interaction
• Resistant Disease: Streptococcus agalactiae inection [ICD-11: FB84.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: C-28/I2 cells; Rib; Homo sapiens (Human); CVCL_0187
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay; qRT-PCR; Western bloting analysis; Enzyme-linked immunosorbent assay; Luciferase assay; RNA immunoprecipitation
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Knockdown of MFI2-AS1 increased cell viability but suppressed apoptosis, inflammatory response and extracellular matrix degradation in LPS-treated chondrocytes by increasing miR-130a-3p and decreasing TCF4, indicating a novel target for the treatment of osteoarthritis.

ICD-19: Perinatal period certain diseases

Neonatal pneumonia [ICD-11: KB24]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (MIAT2) [10]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Neonatal pneumonia [ICD-11: KB24.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: WI-38 cells; Fetal lung; Homo sapiens (Human); CVCL_0579
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Enzyme-linked immunosorbent assay; Mimic
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Long noncoding RNA MIAT2 alleviates lipopolysaccharide-induced inflammatory damage in WI-38 cells by sponging microRNA-15.

ICD-21: Symptoms/clinical signs/unclassified clinical findings

Systemic inflammatory response syndrome [ICD-11: MG46]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Functional intergenic repeating RNA element (Firre) [6]

• Molecule Alteration: Up-regulation; Locus
• Resistant Disease: Systemic inflammatory response syndrome [ICD-11: MG46.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Overexpression assay
• Mechanism Description: The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis.

ICD-22: Injury/poisoning/certain external causes consequences

Acute lung injury [ICD-11: NB32]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Cancer susceptibility 9 (CASC9) [8]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Acute lung injury [ICD-11: NB32.3Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HSAECs; N.A.; .; N.A.
• In Vivo Model: Sepsis rat model; Rattus norvegicus
• Experiment for Molecule Alteration: Knockdown assay; qRT-PCR; Western bloting analysis; Luciferase assay; RIP experiments assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: CASC9 protects lung epithelial cells from sepsis-induced injury via regulating miR-195-5p/PDK4 axis.

Key Molecule: Long non-protein coding RNA (A_30_P01029806) [7]

• Molecule Alteration: Down-regulation; Expression
• Resistant Disease: Acute lung injury [ICD-11: NB32.3Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: ALI mouse model; Mus musculus
• Experiment for Molecule Alteration: Microarray assay
• Experiment for Drug Resistance: CT scan assay
• Mechanism Description: LncRNA A_30_P01029806 and A_30_P01029194, which were down-regulated, were involved in the signaling pathways closely related to ALI.

References

• Ref 1: Long non-coding RNA TUG1 enhances chemosensitivity in non-small cell lung cancer by impairing microRNA-221-dependent PTEN inhibitionAging (Albany NY). 2019 Sep 18;11(18):7553-7569. doi: 10.18632/aging.102271. Epub 2019 Sep 18.
• Ref 2: Knockdown of lncRNA MFI2-AS1 inhibits lipopolysaccharide-induced osteoarthritis progression by miR-130a-3p/TCF4Life Sci. 2020 Jan 1;240:117019. doi: 10.1016/j.lfs.2019.117019. Epub 2019 Oct 31.
• Ref 3: Long non-coding RNA MALAT1 interacts with transcription factor Foxo1 to regulate SIRT1 transcription in high glucose-induced HK-2 cells injuryBiochem Biophys Res Commun. 2018 Sep 5;503(2):849-855. doi: 10.1016/j.bbrc.2018.06.086. Epub 2018 Jul 14.
• Ref 4: LncRNA MEG3 contributes to adenosine-induced cytotoxicity in hepatoma HepG2 cells by downregulated ILF3 and autophagy inhibition via regulation PI3K-AKT-mTOR and beclin-1 signaling pathwayJ Cell Biochem. 2019 Oct;120(10):18172-18185. doi: 10.1002/jcb.29123. Epub 2019 May 29.
• Ref 5: Downregulation of lncRNA H19 sensitizes melanoma cells to cisplatin by regulating the miR-18b/IGF1 axisAnticancer Drugs. 2020 Jun;31(5):473-482. doi: 10.1097/CAD.0000000000000888.
• Ref 6: The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesisNat Commun. 2019 Nov 13;10(1):5137. doi: 10.1038/s41467-019-12970-4.
• Ref 7: LncRNA analysis of lung tissues after hUC-MSCs and FTY720 treatment of lipopolysaccharide-induced acute lung injury in mouse modelsInt Immunopharmacol. 2019 Jun;71:68-75. doi: 10.1016/j.intimp.2019.03.017. Epub 2019 Mar 14.
• Ref 8: Down-regulation of lncRNA CASC9 aggravates sepsis-induced acute lung injury by regulating miR-195-5p/PDK4 axisInflamm Res. 2020 Jun;69(6):559-568. doi: 10.1007/s00011-020-01316-2. Epub 2020 Mar 27.
• Ref 9: Intranasal Delivery of lincRNA-Cox2 siRNA Loaded Extracellular Vesicles Decreases Lipopolysaccharide-Induced Microglial Proliferation in MiceJ Neuroimmune Pharmacol. 2020 Sep;15(3):390-399. doi: 10.1007/s11481-019-09864-z. Epub 2019 Jul 20.
• Ref 10: Long noncoding RNA MIAT2 alleviates lipopolysaccharide-induced inflammatory damage in WI-38 cells by sponging microRNA-15J Cell Physiol. 2020 Apr;235(4):3690-3697. doi: 10.1002/jcp.29263. Epub 2019 Sep 30.
• Ref 11: Sinomenine retards LPS-elicited inflammation via down-regulating CCAT1 in HaCaT cellsLife Sci. 2019 Sep 15;233:116703. doi: 10.1016/j.lfs.2019.116703. Epub 2019 Jul 26.
• Ref 12: NEAT1 regulates MPP(+)-induced neuronal injury by targeting miR-124 in neuroblastoma cellsNeurosci Lett. 2019 Aug 24;708:134340. doi: 10.1016/j.neulet.2019.134340. Epub 2019 Jun 19.