Structure

Physi-Chem Properties

Molecular Weight:  372.08
Volume:  358.104
LogP:  1.485
LogD:  1.34
LogS:  -3.167
# Rotatable Bonds:  4
TPSA:  141.36
# H-Bond Aceptor:  8
# H-Bond Donor:  4
# Rings:  3
# Heavy Atoms:  8

MedChem Properties

QED Drug-Likeness Score:  0.44
Synthetic Accessibility Score:  3.739
Fsp3:  0.211
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -5.419
MDCK Permeability:  3.2253821700578555e-05
Pgp-inhibitor:  0.003
Pgp-substrate:  0.926
Human Intestinal Absorption (HIA):  0.024
20% Bioavailability (F20%):  0.003
30% Bioavailability (F30%):  0.05

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.255
Plasma Protein Binding (PPB):  82.2765884399414%
Volume Distribution (VD):  0.518
Pgp-substrate:  21.240434646606445%

ADMET: Metabolism

CYP1A2-inhibitor:  0.033
CYP1A2-substrate:  0.83
CYP2C19-inhibitor:  0.115
CYP2C19-substrate:  0.112
CYP2C9-inhibitor:  0.096
CYP2C9-substrate:  0.357
CYP2D6-inhibitor:  0.008
CYP2D6-substrate:  0.14
CYP3A4-inhibitor:  0.405
CYP3A4-substrate:  0.584

ADMET: Excretion

Clearance (CL):  2.761
Half-life (T1/2):  0.16

ADMET: Toxicity

hERG Blockers:  0.018
Human Hepatotoxicity (H-HT):  0.168
Drug-inuced Liver Injury (DILI):  0.934
AMES Toxicity:  0.181
Rat Oral Acute Toxicity:  0.294
Maximum Recommended Daily Dose:  0.021
Skin Sensitization:  0.111
Carcinogencity:  0.336
Eye Corrosion:  0.003
Eye Irritation:  0.012
Respiratory Toxicity:  0.232

Download Data

Data Type Select
General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC59751

Natural Product ID:  NPC59751
Common Name*:   8-Demethylgeldanamycin
IUPAC Name:   [(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-6-hydroxy-5,11,21-trimethoxy-3,7,15-trimethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate
Synonyms:   8-Demethylgeldanamycin
Standard InCHIKey:  HHCQVBCBDZQDKS-KNWAINQHSA-N
Standard InCHI:  InChI=1S/C28H38N2O9/c1-15-12-18-25(33)19(14-20(31)26(18)38-6)30-27(34)17(3)8-7-9-21(36-4)22(39-28(29)35)11-10-16(2)24(32)23(13-15)37-5/h7-11,14-16,21-24,32H,12-13H2,1-6H3,(H2,29,35)(H,30,34)/b9-7-,11-10+,17-8+/t15-,16+,21+,22+,23+,24-/m1/s1
SMILES:  CO[C@H]1C[C@H](C)CC2=C(OC)C(=O)C=C(C2=O)N=C(O)/C(=C/C=C[C@@H]([C@H](/C=C/[C@@H]([C@H]1O)C)OC(=N)O)OC)/C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL464370
PubChem CID:   11519596
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000064] Macrolactams

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[14563159]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[15844961]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[16378365]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[16453790]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[16724461]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[17632514]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[19231864]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[21486005]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[21504214]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[24224794]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[3170341]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[3819734]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[5549382]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[TCMID]
NPO13391 Streptomyces hygroscopicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  NP Quantity Composition/Concentration

Organism ID NP ID Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  Biological Activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT134 Cell Line SK-BR-3 Homo sapiens IC50 = 481.0 nM PMID[509097]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC59751 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC271621
1.0 High Similarity NPC27413
0.972 High Similarity NPC5485
0.9541 High Similarity NPC315652
0.9541 High Similarity NPC7905
0.9375 High Similarity NPC473808
0.9292 High Similarity NPC315915
0.9027 High Similarity NPC296361
0.8772 High Similarity NPC316325
0.843 Intermediate Similarity NPC473249
0.7692 Intermediate Similarity NPC133729
0.7652 Intermediate Similarity NPC472616
0.7586 Intermediate Similarity NPC472615
0.7373 Intermediate Similarity NPC251330
0.7273 Intermediate Similarity NPC170375
0.7143 Intermediate Similarity NPC154601
0.7143 Intermediate Similarity NPC314361
0.7143 Intermediate Similarity NPC271269
0.7 Intermediate Similarity NPC469494
0.6967 Remote Similarity NPC24389
0.696 Remote Similarity NPC471645
0.6957 Remote Similarity NPC205546
0.6957 Remote Similarity NPC189764
0.6957 Remote Similarity NPC50902
0.6957 Remote Similarity NPC233273
0.6937 Remote Similarity NPC472614
0.6897 Remote Similarity NPC175614
0.685 Remote Similarity NPC476190
0.6829 Remote Similarity NPC133625
0.6783 Remote Similarity NPC316249
0.6769 Remote Similarity NPC469515
0.6748 Remote Similarity NPC307903
0.6748 Remote Similarity NPC140251
0.6721 Remote Similarity NPC469852
0.6716 Remote Similarity NPC477793
0.6716 Remote Similarity NPC329919
0.6695 Remote Similarity NPC472162
0.6695 Remote Similarity NPC472166
0.6695 Remote Similarity NPC265662
0.6667 Remote Similarity NPC469853
0.6667 Remote Similarity NPC469865
0.6667 Remote Similarity NPC110294
0.6639 Remote Similarity NPC161855
0.6638 Remote Similarity NPC472613
0.6612 Remote Similarity NPC473596
0.661 Remote Similarity NPC288350
0.661 Remote Similarity NPC173329
0.6589 Remote Similarity NPC475642
0.6585 Remote Similarity NPC472749
0.6585 Remote Similarity NPC472751
0.6581 Remote Similarity NPC116930
0.6571 Remote Similarity NPC230889
0.6555 Remote Similarity NPC472167
0.6535 Remote Similarity NPC476269
0.6529 Remote Similarity NPC175531
0.6529 Remote Similarity NPC313234
0.6519 Remote Similarity NPC262845
0.6519 Remote Similarity NPC68293
0.6518 Remote Similarity NPC161670
0.6508 Remote Similarity NPC122926
0.6508 Remote Similarity NPC113012
0.6504 Remote Similarity NPC472748
0.6496 Remote Similarity NPC475098
0.6496 Remote Similarity NPC189651
0.6491 Remote Similarity NPC45409
0.6475 Remote Similarity NPC128501
0.6475 Remote Similarity NPC469598
0.6471 Remote Similarity NPC165332
0.6471 Remote Similarity NPC180722
0.6471 Remote Similarity NPC195645
0.6471 Remote Similarity NPC473291
0.6466 Remote Similarity NPC471399
0.6466 Remote Similarity NPC475879
0.6457 Remote Similarity NPC29501
0.6441 Remote Similarity NPC121825
0.6441 Remote Similarity NPC5418
0.6429 Remote Similarity NPC477786
0.6429 Remote Similarity NPC477784
0.6429 Remote Similarity NPC477785
0.6429 Remote Similarity NPC473578
0.6429 Remote Similarity NPC298484
0.6423 Remote Similarity NPC474563
0.6423 Remote Similarity NPC472747
0.6423 Remote Similarity NPC472750
0.6418 Remote Similarity NPC16709
0.641 Remote Similarity NPC472010
0.6406 Remote Similarity NPC66108
0.6404 Remote Similarity NPC316426
0.6404 Remote Similarity NPC472009
0.6404 Remote Similarity NPC315395
0.6393 Remote Similarity NPC469851
0.6393 Remote Similarity NPC316250
0.6391 Remote Similarity NPC156379
0.6391 Remote Similarity NPC475383
0.6378 Remote Similarity NPC477997
0.6378 Remote Similarity NPC476290
0.6364 Remote Similarity NPC471672
0.6364 Remote Similarity NPC313911
0.6364 Remote Similarity NPC314854
0.6364 Remote Similarity NPC475653
0.6357 Remote Similarity NPC78189
0.6356 Remote Similarity NPC469645
0.6356 Remote Similarity NPC469692
0.6349 Remote Similarity NPC475150
0.6348 Remote Similarity NPC472007
0.6348 Remote Similarity NPC300779
0.6333 Remote Similarity NPC255410
0.6328 Remote Similarity NPC475608
0.6328 Remote Similarity NPC21713
0.6325 Remote Similarity NPC166554
0.6325 Remote Similarity NPC474098
0.6325 Remote Similarity NPC475995
0.6325 Remote Similarity NPC265856
0.632 Remote Similarity NPC201128
0.6303 Remote Similarity NPC477241
0.6303 Remote Similarity NPC65829
0.6296 Remote Similarity NPC315783
0.6293 Remote Similarity NPC116231
0.6293 Remote Similarity NPC60765
0.6293 Remote Similarity NPC475739
0.6293 Remote Similarity NPC472008
0.629 Remote Similarity NPC472755
0.6283 Remote Similarity NPC471595
0.6283 Remote Similarity NPC16488
0.6281 Remote Similarity NPC208094
0.6281 Remote Similarity NPC20066
0.6281 Remote Similarity NPC239895
0.6281 Remote Similarity NPC120299
0.6273 Remote Similarity NPC231739
0.6261 Remote Similarity NPC472161
0.6261 Remote Similarity NPC164393
0.625 Remote Similarity NPC204639
0.625 Remote Similarity NPC300710
0.625 Remote Similarity NPC272050
0.6241 Remote Similarity NPC241050
0.6239 Remote Similarity NPC51358
0.6239 Remote Similarity NPC307092
0.6239 Remote Similarity NPC295448
0.6239 Remote Similarity NPC212598
0.623 Remote Similarity NPC203627
0.623 Remote Similarity NPC166770
0.623 Remote Similarity NPC300584
0.6228 Remote Similarity NPC70424
0.6228 Remote Similarity NPC243618
0.6222 Remote Similarity NPC290261
0.622 Remote Similarity NPC473807
0.6214 Remote Similarity NPC101372
0.621 Remote Similarity NPC189609
0.621 Remote Similarity NPC197835
0.621 Remote Similarity NPC303653
0.621 Remote Similarity NPC140591
0.621 Remote Similarity NPC291500
0.621 Remote Similarity NPC472754
0.6195 Remote Similarity NPC477487
0.6186 Remote Similarity NPC145666
0.6186 Remote Similarity NPC477866
0.6186 Remote Similarity NPC477865
0.6182 Remote Similarity NPC473536
0.6179 Remote Similarity NPC215253
0.6179 Remote Similarity NPC475053
0.6179 Remote Similarity NPC185253
0.6174 Remote Similarity NPC187529
0.6174 Remote Similarity NPC471494
0.6172 Remote Similarity NPC38154
0.6154 Remote Similarity NPC106051
0.6154 Remote Similarity NPC473658
0.6154 Remote Similarity NPC53454
0.6154 Remote Similarity NPC316186
0.6154 Remote Similarity NPC26078
0.6148 Remote Similarity NPC266842
0.6148 Remote Similarity NPC471694
0.6147 Remote Similarity NPC315552
0.6142 Remote Similarity NPC315531
0.6142 Remote Similarity NPC266514
0.6134 Remote Similarity NPC32552
0.6134 Remote Similarity NPC314500
0.6131 Remote Similarity NPC160493
0.6129 Remote Similarity NPC110443
0.6129 Remote Similarity NPC472753
0.6129 Remote Similarity NPC128733
0.6129 Remote Similarity NPC46998
0.6129 Remote Similarity NPC133907
0.6129 Remote Similarity NPC185141
0.6121 Remote Similarity NPC234038
0.6121 Remote Similarity NPC261721
0.6121 Remote Similarity NPC472136
0.6121 Remote Similarity NPC311163
0.6119 Remote Similarity NPC313802
0.6119 Remote Similarity NPC67917
0.6119 Remote Similarity NPC314268
0.6119 Remote Similarity NPC477515
0.6116 Remote Similarity NPC295347
0.6111 Remote Similarity NPC74035
0.6111 Remote Similarity NPC472756
0.6107 Remote Similarity NPC469496
0.6107 Remote Similarity NPC469454
0.6107 Remote Similarity NPC469463
0.6106 Remote Similarity NPC112868
0.6106 Remote Similarity NPC275766
0.6102 Remote Similarity NPC471054

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC59751 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.9533 High Similarity NPD7116 Clinical (unspecified phase)
0.887 High Similarity NPD7299 Clinical (unspecified phase)
0.8772 High Similarity NPD7500 Approved
0.8718 High Similarity NPD7623 Phase 3
0.8718 High Similarity NPD7624 Clinical (unspecified phase)
0.843 Intermediate Similarity NPD7747 Phase 1
0.843 Intermediate Similarity NPD7746 Phase 1
0.8319 Intermediate Similarity NPD7739 Clinical (unspecified phase)
0.7273 Intermediate Similarity NPD7601 Clinical (unspecified phase)
0.6719 Remote Similarity NPD7505 Discontinued
0.6471 Remote Similarity NPD7839 Suspended
0.633 Remote Similarity NPD4756 Discovery
0.6296 Remote Similarity NPD7829 Approved
0.6296 Remote Similarity NPD7830 Approved
0.625 Remote Similarity NPD6421 Discontinued
0.623 Remote Similarity NPD8029 Clinical (unspecified phase)
0.6186 Remote Similarity NPD6698 Approved
0.6186 Remote Similarity NPD46 Approved
0.6172 Remote Similarity NPD6413 Approved
0.6165 Remote Similarity NPD7641 Discontinued
0.6159 Remote Similarity NPD8074 Phase 3
0.6148 Remote Similarity NPD8444 Approved
0.614 Remote Similarity NPD6110 Phase 1
0.6099 Remote Similarity NPD7260 Phase 2
0.605 Remote Similarity NPD7838 Discovery
0.6028 Remote Similarity NPD6914 Discontinued
0.6 Remote Similarity NPD7983 Approved
0.5971 Remote Similarity NPD8273 Phase 1
0.5942 Remote Similarity NPD7642 Approved
0.5917 Remote Similarity NPD5785 Approved
0.5878 Remote Similarity NPD6420 Discontinued
0.5862 Remote Similarity NPD8415 Approved
0.5862 Remote Similarity NPD7154 Phase 3
0.5857 Remote Similarity NPD4816 Clinical (unspecified phase)
0.5833 Remote Similarity NPD8413 Clinical (unspecified phase)
0.5833 Remote Similarity NPD6845 Suspended
0.5822 Remote Similarity NPD8387 Clinical (unspecified phase)
0.5794 Remote Similarity NPD6404 Discontinued
0.5781 Remote Similarity NPD2258 Approved
0.5781 Remote Similarity NPD2259 Approved
0.5763 Remote Similarity NPD5363 Approved
0.5755 Remote Similarity NPD8080 Discontinued
0.5745 Remote Similarity NPD8451 Approved
0.5739 Remote Similarity NPD8259 Clinical (unspecified phase)
0.5725 Remote Similarity NPD6686 Approved
0.5704 Remote Similarity NPD8448 Approved
0.5701 Remote Similarity NPD3704 Approved
0.5701 Remote Similarity NPD6108 Clinical (unspecified phase)
0.5694 Remote Similarity NPD8391 Approved
0.5694 Remote Similarity NPD8392 Approved
0.5694 Remote Similarity NPD8390 Approved
0.5691 Remote Similarity NPD5779 Approved
0.5691 Remote Similarity NPD5778 Approved
0.5674 Remote Similarity NPD8341 Approved
0.5674 Remote Similarity NPD8342 Approved
0.5674 Remote Similarity NPD8340 Approved
0.5674 Remote Similarity NPD8299 Approved
0.5649 Remote Similarity NPD7899 Clinical (unspecified phase)
0.5634 Remote Similarity NPD5108 Clinical (unspecified phase)
0.562 Remote Similarity NPD7115 Discovery

  Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data