Drug Information

Drug (ID: DG01847) and It's Reported Resistant Information

• Name: Insulin recombinant
• Synonyms: 9004-10-8; Iletin; Endopancrine; Decurvon; Dermulin; Humilin; Insular; Insulyl; Iszilin; Musulin; insulin-human; Dal-insulinum; Intesulin B; AERx; Insulin, dalanated; Insulina dalanatada; Insulinum dalanatum; Imusay-131; INSULIN INJECTION; Dalanated insulin [INN]; Insulina iniettabile neutra; Insulini injectio neutralis; Injectable insulini neutrale; Inyectable neutro de insulina; CCRIS 5464; HSDB 3102; Insulin, dalanated [USAN:INN]; Insulinum dalanatum [INN-Latin]; AERx [Insulin management system]; Insulina dalanatada [INN-Spanish]; Solute neutre injectable d'insuline; HMR 4006; Insulina iniettabile neutra [DCIT]; EINECS 232-672-8; S.N. 44; Insulini injectio neutralis [INN-Latin]; Inyectable neutro de insulina [INN-Spanish]; Solute neutre injectable d'insuline [INN-French]
• Indication:
  In total 1 Indication(s)
  Diabetic complication [ICD-11: 5A2Y]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Polycystic ovary syndrome [ICD-11: 5A80]; [2]
  Type 2 diabetes mellitus [ICD-11: 5A11]; [3]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Type 2 diabetes mellitus [ICD-11: 5A11]; [4]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
  Type 2 diabetes mellitus [ICD-11: 5A11]; [5]
• Target: Insulin receptor (INSR); INSR_HUMAN; [1]
• Formula: 178
• IsoSMILES: CC[C@@H](C)[C@H]1C(=O)N[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC5=CC=CC=C5)C(=O)N[C@@H](CC6=CC=CC=C6)C(=O)N[C@@H](CC7=CC=C(C=C7)O)C(=O)N[C@@H]([C@H](C)O)C(=O)N8CCC[C@H]8C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@H](C)O)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CO)[C@H](C)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@H](C)CC)NC(=O)CN
• InChI: InChI=1S/C256H381N65O77S6/c1-29-130(23)202(311-190(337)103-258)250(391)315-200(128(19)20)246(387)286-158(75-82-197(347)348)216(357)281-154(70-77-186(261)333)220(361)306-181-115-402-403-116-182-241(382)303-176(110-323)238(379)293-161(88-122(7)8)224(365)294-167(95-139-53-61-145(328)62-54-139)227(368)282-153(69-76-185(260)332)217(358)289-160(87-121(5)6)222(363)283-157(74-81-196(345)346)219(360)301-173(101-188(263)335)233(374)297-169(97-141-57-65-147(330)66-58-141)230(371)307-180(240(381)302-174(254(395)396)102-189(264)336)114-401-400-113-179(213(354)272-106-191(338)277-152(72-79-194(341)342)215(356)280-150(51-42-84-270-256(266)267)211(352)271-107-192(339)278-165(93-137-46-36-32-37-47-137)226(367)296-166(94-138-48-38-33-39-49-138)229(370)298-170(98-142-59-67-148(331)68-60-142)236(377)318-205(134(27)326)253(394)321-85-43-52-184(321)244(385)284-151(50-40-41-83-257)221(362)319-206(135(28)327)255(397)398)309-247(388)199(127(17)18)314-234(375)163(90-124(11)12)291-228(369)168(96-140-55-63-146(329)64-56-140)295-223(364)159(86-120(3)4)288-209(350)132(25)276-214(355)156(73-80-195(343)344)285-245(386)198(126(15)16)313-235(376)164(91-125(13)14)292-232(373)172(100-144-105-269-119-275-144)300-237(378)175(109-322)279-193(340)108-273-212(353)178(112-399-404-117-183(308-242(181)383)243(384)317-204(133(26)325)251(392)304-177(111-324)239(380)316-203(131(24)30-2)249(390)310-182)305-225(366)162(89-123(9)10)290-231(372)171(99-143-104-268-118-274-143)299-218(359)155(71-78-187(262)334)287-252(393)207(208(265)349)320-248(389)201(129(21)22)312-210(351)149(259)92-136-44-34-31-35-45-136/h31-39,44-49,53-68,104-105,118-135,149-184,198-207,322-331H,29-30,40-43,50-52,69-103,106-117,257-259H2,1-28H3,(H2,260,332)(H2,261,333)(H2,262,334)(H2,263,335)(H2,264,336)(H2,265,349)(H,268,274)(H,269,275)(H,271,352)(H,272,354)(H,273,353)(H,276,355)(H,277,338)(H,278,339)(H,279,340)(H,280,356)(H,281,357)(H,282,368)(H,283,363)(H,284,385)(H,285,386)(H,286,387)(H,287,393)(H,288,350)(H,289,358)(H,290,372)(H,291,369)(H,292,373)(H,293,379)(H,294,365)(H,295,364)(H,296,367)(H,297,374)(H,298,370)(H,299,359)(H,300,378)(H,301,360)(H,302,381)(H,303,382)(H,304,392)(H,305,366)(H,306,361)(H,307,371)(H,308,383)(H,309,388)(H,310,390)(H,311,337)(H,312,351)(H,313,376)(H,314,375)(H,315,391)(H,316,380)(H,317,384)(H,318,377)(H,319,362)(H,320,389)(H,341,342)(H,343,344)(H,345,346)(H,347,348)(H,395,396)(H,397,398)(H4,266,267,270)/t130-,131-,132+,133+,134+,135+,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+,198+,199+,200+,201+,202+,203+,204+,205+,206+,207+/m1/s1
• InChIKey: YAJCHEVQCOHZDC-QMMNLEPNSA-N
• PubChem CID: 70678557
• TTD Drug ID: D06SVW
• INTEDE ID: DR00408
• DrugBank ID: DB00030

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-02: Benign/in-situ/malignant neoplasm

Breast cancer [ICD-11: 2C60]

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) [1]

• Molecule Alteration: .; Expression
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: qRT-PCR; RNA pull down assay; RIP experiments assay; Co-IP; Western bloting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MALAT1 binding competes with the interaction between sirtuin1 (SIRT1) and DBC1, which then releases SIRT1 and enhances its deacetylation activity.

ICD-05: Endocrine/nutritional/metabolic diseases

Type 2 diabetes mellitus [ICD-11: 5A11]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (UC.333) [3]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vivo Model: Male db/db mice;C57BL/6 mice model; Mus musculus
• Experiment for Molecule Alteration: Microarray assay; Western bloting analysis; Fluorescence in situ hybridization; Overexpression assay; Knockdown assay
• Mechanism Description: Ultraconserved element uc.333 increases insulin sensitivity by binding to miR-223.

Key Molecule: Long non-protein coding RNA (UC.333) [3]

• Molecule Alteration: Down-regulation; Interaction
• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vivo Model: Male db/db mice;C57BL/6 mice model; Mus musculus
• Experiment for Molecule Alteration: Microarray assay; Western bloting analysis; Fluorescence in situ hybridization; Overexpression assay; Knockdown assay
• Mechanism Description: UC.333 improves IR by binding to miR-223; thus, uc.333 may be a useful target for the treatment and prevention of IR.

Key Molecule: Long non-protein coding RNA (RISA) [5]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: C2C12 cells; Skeletal muscle; Homo sapiens (Human); CVCL_0188
• In Vivo Model: Male C57BL/6 mice model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay
• Mechanism Description: Risa regulates insulin sensitivity by affecting autophagy and suggest that Risa is a potential target for treating insulin-resistance-related diseases.

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [6]

• Molecule Alteration: Down-regulation; Expression
• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: RAP-PCR; qRT-PCR
• Mechanism Description: The overall metabolic impact of the absence of Malat1 on adipose tissue accretion and glucose intolerance is either physiologically not relevant upon aging and obesity, or that it is masked by as yet unknown compensatory mechanisms.

Key Molecule: H19, imprinted maternally expressed transcript (H19) [7]

• Molecule Alteration: Down-regulation; Expression
• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Drug Resistance: Glucose tolerance test assay
• Mechanism Description: H19 LncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting AMPK.

Key Molecule: Matrin 3, pseudogene 2 (Matr3-ps2) [4]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: C2C12 cells; Skeletal muscle; Homo sapiens (Human); CVCL_0188
• In Vivo Model: Male C57BLKS/J db/db mice model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: ENSMUST00000160839 was up-regulated in the PA-treated C2C12 myotubes compared with the control cells via qPCR detection.

Polycystic ovary syndrome [ICD-11: 5A80]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: BRAF-activated non-protein coding RNA (BANCR) [2]

• Molecule Alteration: Up-regulation; Expression
• Resistant Disease: Polycystic ovary syndrome [ICD-11: 5A80.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human polycystic ovary syndrome cell isolates; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA BANCR participates in polycystic ovary syndrome by promoting cell apoptosis.

References

• Ref 1: 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 2: LncRNA BANCR participates in polycystic ovary syndrome by promoting cell apoptosisMol Med Rep. 2019 Mar;19(3):1581-1586. doi: 10.3892/mmr.2018.9793. Epub 2018 Dec 24.
• Ref 3: Ultraconserved element uc.333 increases insulin sensitivity by binding to miR-223Aging (Albany NY). 2020 Apr 17;12(8):6667-6679. doi: 10.18632/aging.103020. Epub 2020 Apr 17.
• Ref 4: RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cellsBiosci Rep. 2020 Jan 31;40(1):BSR20192523. doi: 10.1042/BSR20192523.
• Ref 5: Down-regulation of Risa improves insulin sensitivity by enhancing autophagyFASEB J. 2016 Sep;30(9):3133-45. doi: 10.1096/fj.201500058R. Epub 2016 Jun 1.
• Ref 6: Loss of Malat1 does not modify age- or diet-induced adipose tissue accretion and insulin resistance in micePLoS One. 2018 May 10;13(5):e0196603. doi: 10.1371/journal.pone.0196603. eCollection 2018.
• Ref 7: H19 lncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting AMPKDiabetes. 2018 Nov;67(11):2183-2198. doi: 10.2337/db18-0370. Epub 2018 Sep 10.