Structure

Physi-Chem Properties

Molecular Weight:  643.33
Volume:  635.021
LogP:  1.447
LogD:  0.765
LogS:  -3.09
# Rotatable Bonds:  7
TPSA:  165.66
# H-Bond Aceptor:  13
# H-Bond Donor:  3
# Rings:  2
# Heavy Atoms:  14

MedChem Properties

QED Drug-Likeness Score:  0.269
Synthetic Accessibility Score:  5.423
Fsp3:  0.8
Lipinski Rule-of-5:  Rejected
Pfizer Rule:  Accepted
GSK Rule:  Rejected
BMS Rule:  1
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -5.517
MDCK Permeability:  8.861882088240236e-05
Pgp-inhibitor:  0.43
Pgp-substrate:  0.99
Human Intestinal Absorption (HIA):  0.977
20% Bioavailability (F20%):  0.82
30% Bioavailability (F30%):  0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.191
Plasma Protein Binding (PPB):  75.83978271484375%
Volume Distribution (VD):  0.46
Pgp-substrate:  33.41397476196289%

ADMET: Metabolism

CYP1A2-inhibitor:  0.001
CYP1A2-substrate:  0.057
CYP2C19-inhibitor:  0.035
CYP2C19-substrate:  0.509
CYP2C9-inhibitor:  0.015
CYP2C9-substrate:  0.07
CYP2D6-inhibitor:  0.007
CYP2D6-substrate:  0.086
CYP3A4-inhibitor:  0.564
CYP3A4-substrate:  0.582

ADMET: Excretion

Clearance (CL):  5.039
Half-life (T1/2):  0.886

ADMET: Toxicity

hERG Blockers:  0.003
Human Hepatotoxicity (H-HT):  0.927
Drug-inuced Liver Injury (DILI):  0.615
AMES Toxicity:  0.007
Rat Oral Acute Toxicity:  0.507
Maximum Recommended Daily Dose:  0.889
Skin Sensitization:  0.087
Carcinogencity:  0.01
Eye Corrosion:  0.003
Eye Irritation:  0.005
Respiratory Toxicity:  0.013

Download Data

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

  Natural Product: NPC475637

Natural Product ID:  NPC475637
Common Name*:   Destruxin-A4 Chlorohydrin
IUPAC Name:   (10S,13S,16S,19S)-13,16-bis[(2S)-butan-2-yl]-3-(3-chloro-2-hydroxypropyl)-10,11,14-trimethyl-4-oxa-1,8,11,14,17-pentazabicyclo[17.3.0]docosane-2,5,9,12,15,18-hexone
Synonyms:   Destruxin-A4 Chlorohydrin
Standard InCHIKey:  OHKVAKWSVKDPHP-KORLZQGMSA-N
Standard InCHI:  InChI=1S/C30H50ClN5O8/c1-8-17(3)24-29(42)35(7)25(18(4)9-2)30(43)34(6)19(5)26(39)32-13-12-23(38)44-22(15-20(37)16-31)28(41)36-14-10-11-21(36)27(40)33-24/h17-22,24-25,37H,8-16H2,1-7H3,(H,32,39)(H,33,40)/t17-,18-,19-,20?,21-,22?,24-,25-/m0/s1
SMILES:  ClCC(CC1OC(=O)CCN=C(O)[C@H](C)N(C)C(=O)[C@@H](N(C(=O)[C@@H](N=C([C@H]2N(C1=O)CCC2)O)[C@H](CC)C)C)[C@H](CC)C)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL509978
PubChem CID:   10604207
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0001813] Peptidomimetics
        • [CHEMONTID:0001961] Depsipeptides
          • [CHEMONTID:0001994] Cyclic depsipeptides

*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
NPO33484 os-f68576 n.a. n.a. n.a. n.a. n.a. n.a. PMID[9514014]

☑ 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
NPT20904 CELL-LINE Hep 3B2 Homo sapiens Ratio = 28.0 n.a. PMID[507142]
NPT20904 CELL-LINE Hep 3B2 Homo sapiens Activity = 0.2 uM PMID[507142]
NPT20904 CELL-LINE Hep 3B2 Homo sapiens Activity = 36.0 mU/ml PMID[507142]

☑ 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 NPC475637 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
0.9175 High Similarity NPC473597
0.8614 High Similarity NPC475440
0.8571 High Similarity NPC471098
0.8571 High Similarity NPC173763
0.8571 High Similarity NPC62263
0.8469 Intermediate Similarity NPC474576
0.8367 Intermediate Similarity NPC474593
0.8367 Intermediate Similarity NPC475801
0.785 Intermediate Similarity NPC471097
0.785 Intermediate Similarity NPC475149
0.7736 Intermediate Similarity NPC220234
0.7664 Intermediate Similarity NPC13175
0.7664 Intermediate Similarity NPC475791
0.757 Intermediate Similarity NPC475758
0.7545 Intermediate Similarity NPC323720
0.7523 Intermediate Similarity NPC124554
0.7523 Intermediate Similarity NPC5864
0.7523 Intermediate Similarity NPC301148
0.7387 Intermediate Similarity NPC124549
0.7345 Intermediate Similarity NPC67009
0.7297 Intermediate Similarity NPC198344
0.7193 Intermediate Similarity NPC171734
0.71 Intermediate Similarity NPC476302
0.7 Intermediate Similarity NPC476243
0.7 Intermediate Similarity NPC476156
0.7 Intermediate Similarity NPC476117
0.7 Intermediate Similarity NPC476137
0.6916 Remote Similarity NPC477538
0.69 Remote Similarity NPC31756
0.6891 Remote Similarity NPC471202
0.6891 Remote Similarity NPC63191
0.6863 Remote Similarity NPC246005
0.685 Remote Similarity NPC470651
0.685 Remote Similarity NPC470655
0.6765 Remote Similarity NPC470783
0.6765 Remote Similarity NPC475542
0.6759 Remote Similarity NPC476019
0.6735 Remote Similarity NPC178919
0.6724 Remote Similarity NPC241394
0.6699 Remote Similarity NPC84128
0.6699 Remote Similarity NPC53858
0.6667 Remote Similarity NPC50520
0.664 Remote Similarity NPC477238
0.6638 Remote Similarity NPC128303
0.6634 Remote Similarity NPC477145
0.6634 Remote Similarity NPC473741
0.6574 Remote Similarity NPC275715
0.6569 Remote Similarity NPC312315
0.6566 Remote Similarity NPC263281
0.6545 Remote Similarity NPC315237
0.648 Remote Similarity NPC477237
0.646 Remote Similarity NPC134504
0.646 Remote Similarity NPC47076
0.6449 Remote Similarity NPC477539
0.6446 Remote Similarity NPC476875
0.6422 Remote Similarity NPC322966
0.64 Remote Similarity NPC209156
0.6392 Remote Similarity NPC10716
0.6378 Remote Similarity NPC315188
0.6327 Remote Similarity NPC29598
0.6327 Remote Similarity NPC212866
0.6299 Remote Similarity NPC470652
0.6238 Remote Similarity NPC126186
0.6238 Remote Similarity NPC256312
0.6238 Remote Similarity NPC161774
0.6238 Remote Similarity NPC266888
0.6231 Remote Similarity NPC470650
0.6231 Remote Similarity NPC470653
0.6231 Remote Similarity NPC470654
0.622 Remote Similarity NPC469899
0.6214 Remote Similarity NPC59867
0.62 Remote Similarity NPC214532
0.62 Remote Similarity NPC76297
0.62 Remote Similarity NPC196007
0.6186 Remote Similarity NPC314387
0.616 Remote Similarity NPC103391
0.616 Remote Similarity NPC472536
0.6134 Remote Similarity NPC476877
0.6117 Remote Similarity NPC470782
0.6111 Remote Similarity NPC155670
0.6111 Remote Similarity NPC145748
0.6111 Remote Similarity NPC95478
0.6111 Remote Similarity NPC296043
0.61 Remote Similarity NPC478256
0.6063 Remote Similarity NPC329216
0.6055 Remote Similarity NPC227051
0.6033 Remote Similarity NPC476876
0.6019 Remote Similarity NPC327272
0.6 Remote Similarity NPC160688
0.5966 Remote Similarity NPC188785
0.5957 Remote Similarity NPC98424
0.5957 Remote Similarity NPC92784
0.5957 Remote Similarity NPC178662
0.5957 Remote Similarity NPC476133
0.5957 Remote Similarity NPC470884
0.594 Remote Similarity NPC309525
0.5929 Remote Similarity NPC477729
0.5893 Remote Similarity NPC52533
0.5887 Remote Similarity NPC471264
0.5887 Remote Similarity NPC471265
0.5882 Remote Similarity NPC470781
0.5825 Remote Similarity NPC141325
0.5818 Remote Similarity NPC472351
0.581 Remote Similarity NPC476130
0.581 Remote Similarity NPC476324
0.5806 Remote Similarity NPC296143
0.5806 Remote Similarity NPC207820
0.5784 Remote Similarity NPC476291
0.5781 Remote Similarity NPC259586
0.5769 Remote Similarity NPC43219
0.5769 Remote Similarity NPC138435
0.5758 Remote Similarity NPC160661
0.5753 Remote Similarity NPC5620
0.5753 Remote Similarity NPC209509
0.5746 Remote Similarity NPC36254
0.5743 Remote Similarity NPC471820
0.5743 Remote Similarity NPC471821
0.5743 Remote Similarity NPC240848
0.5743 Remote Similarity NPC306696
0.5736 Remote Similarity NPC470621
0.5736 Remote Similarity NPC222481
0.5727 Remote Similarity NPC235078
0.5714 Remote Similarity NPC273185
0.5714 Remote Similarity NPC86064
0.5701 Remote Similarity NPC233108
0.57 Remote Similarity NPC84182
0.57 Remote Similarity NPC128005
0.5686 Remote Similarity NPC322274
0.5678 Remote Similarity NPC117829
0.5673 Remote Similarity NPC29326
0.5664 Remote Similarity NPC477728
0.5655 Remote Similarity NPC269398
0.5655 Remote Similarity NPC469426
0.5655 Remote Similarity NPC263493
0.5655 Remote Similarity NPC469427
0.5649 Remote Similarity NPC297145
0.5649 Remote Similarity NPC197743
0.5641 Remote Similarity NPC226513
0.5636 Remote Similarity NPC184473
0.5631 Remote Similarity NPC476285
0.5629 Remote Similarity NPC162104
0.562 Remote Similarity NPC233932
0.5614 Remote Similarity NPC473495
0.5612 Remote Similarity NPC120335
0.56 Remote Similarity NPC129666

  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 NPC475637 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
0.7238 Intermediate Similarity NPD4261 Phase 1
0.7156 Intermediate Similarity NPD8038 Phase 2
0.6923 Remote Similarity NPD7760 Phase 2
0.6923 Remote Similarity NPD7759 Phase 2
0.6842 Remote Similarity NPD6122 Discontinued
0.6818 Remote Similarity NPD7841 Clinical (unspecified phase)
0.6694 Remote Similarity NPD7915 Approved
0.6694 Remote Similarity NPD7916 Approved
0.6636 Remote Similarity NPD3177 Phase 3
0.6606 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6602 Remote Similarity NPD7762 Phase 2
0.6602 Remote Similarity NPD7763 Phase 2
0.6449 Remote Similarity NPD3723 Clinical (unspecified phase)
0.6327 Remote Similarity NPD7840 Approved
0.6226 Remote Similarity NPD1125 Discovery
0.6226 Remote Similarity NPD2683 Discontinued
0.6186 Remote Similarity NPD3184 Approved
0.6186 Remote Similarity NPD3185 Approved
0.6186 Remote Similarity NPD3182 Approved
0.6186 Remote Similarity NPD3183 Approved
0.6121 Remote Similarity NPD3714 Approved
0.6121 Remote Similarity NPD3713 Approved
0.6121 Remote Similarity NPD3715 Approved
0.6017 Remote Similarity NPD6120 Clinical (unspecified phase)
0.5968 Remote Similarity NPD3188 Approved
0.5963 Remote Similarity NPD3733 Clinical (unspecified phase)
0.5818 Remote Similarity NPD9577 Approved
0.569 Remote Similarity NPD6699 Clinical (unspecified phase)
0.5645 Remote Similarity NPD1385 Discontinued
0.5631 Remote Similarity NPD2220 Clinical (unspecified phase)
0.5607 Remote Similarity NPD2689 Clinical (unspecified phase)
0.5603 Remote Similarity NPD2682 Approved
0.56 Remote Similarity NPD6937 Approved

  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