Structure

Physi-Chem Properties

Molecular Weight:  577.35
Volume:  591.087
LogP:  1.512
LogD:  1.078
LogS:  -2.582
# Rotatable Bonds:  5
TPSA:  145.43
# H-Bond Aceptor:  12
# H-Bond Donor:  2
# Rings:  2
# Heavy Atoms:  12

MedChem Properties

QED Drug-Likeness Score:  0.364
Synthetic Accessibility Score:  5.12
Fsp3:  0.724
Lipinski Rule-of-5:  Rejected
Pfizer Rule:  Accepted
GSK Rule:  Rejected
BMS Rule:  0
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -5.282
MDCK Permeability:  9.46495492826216e-06
Pgp-inhibitor:  0.908
Pgp-substrate:  0.746
Human Intestinal Absorption (HIA):  0.917
20% Bioavailability (F20%):  0.019
30% Bioavailability (F30%):  0.846

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.26
Plasma Protein Binding (PPB):  60.02756881713867%
Volume Distribution (VD):  0.406
Pgp-substrate:  44.37837219238281%

ADMET: Metabolism

CYP1A2-inhibitor:  0.001
CYP1A2-substrate:  0.054
CYP2C19-inhibitor:  0.035
CYP2C19-substrate:  0.311
CYP2C9-inhibitor:  0.032
CYP2C9-substrate:  0.1
CYP2D6-inhibitor:  0.009
CYP2D6-substrate:  0.104
CYP3A4-inhibitor:  0.771
CYP3A4-substrate:  0.531

ADMET: Excretion

Clearance (CL):  5.0
Half-life (T1/2):  0.855

ADMET: Toxicity

hERG Blockers:  0.002
Human Hepatotoxicity (H-HT):  0.719
Drug-inuced Liver Injury (DILI):  0.837
AMES Toxicity:  0.008
Rat Oral Acute Toxicity:  0.338
Maximum Recommended Daily Dose:  0.373
Skin Sensitization:  0.054
Carcinogencity:  0.008
Eye Corrosion:  0.003
Eye Irritation:  0.005
Respiratory Toxicity:  0.026

Download Data

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

  Natural Product: NPC475149

Natural Product ID:  NPC475149
Common Name*:   Destruxin-A
IUPAC Name:   (10S,13S,16S,19S)-16-[(2S)-butan-2-yl]-10,11,14-trimethyl-13-propan-2-yl-3-prop-2-enyl-4-oxa-1,8,11,14,17-pentazabicyclo[17.3.0]docosane-2,5,9,12,15,18-hexone
Synonyms:   Destruxin-A
Standard InCHIKey:  XIYSEKITPHTMJT-KKZPJJIVSA-N
Standard InCHI:  InChI=1S/C29H47N5O7/c1-9-12-21-27(38)34-16-11-13-20(34)26(37)31-23(18(5)10-2)28(39)33(8)24(17(3)4)29(40)32(7)19(6)25(36)30-15-14-22(35)41-21/h9,17-21,23-24H,1,10-16H2,2-8H3,(H,30,36)(H,31,37)/t18-,19-,20-,21?,23-,24-/m0/s1
SMILES:  C=CCC1OC(=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(C)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL499433
PubChem CID:   9919947
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
NPT2 Others Unspecified Ratio = 28 n.a. PMID[19161316]
NPT2 Others Unspecified Activity = 0.4 nM PMID[25136754]
NPT2 Others Unspecified Activity = 37 mU/ml PMID[25136754]

☑ 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 NPC475149 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 NPC471097
0.9787 High Similarity NPC13175
0.9787 High Similarity NPC475791
0.9681 High Similarity NPC475758
0.8842 High Similarity NPC471098
0.8842 High Similarity NPC173763
0.8842 High Similarity NPC62263
0.8737 High Similarity NPC474576
0.8632 High Similarity NPC475801
0.8632 High Similarity NPC474593
0.8558 High Similarity NPC171734
0.8137 Intermediate Similarity NPC475440
0.785 Intermediate Similarity NPC475637
0.7658 Intermediate Similarity NPC476875
0.7619 Intermediate Similarity NPC220234
0.7593 Intermediate Similarity NPC323720
0.7429 Intermediate Similarity NPC473597
0.7407 Intermediate Similarity NPC301148
0.7407 Intermediate Similarity NPC5864
0.7407 Intermediate Similarity NPC124554
0.7339 Intermediate Similarity NPC476877
0.7273 Intermediate Similarity NPC124549
0.7227 Intermediate Similarity NPC315188
0.7209 Intermediate Similarity NPC98424
0.7209 Intermediate Similarity NPC178662
0.7209 Intermediate Similarity NPC470884
0.7209 Intermediate Similarity NPC92784
0.7209 Intermediate Similarity NPC476133
0.7207 Intermediate Similarity NPC476876
0.7182 Intermediate Similarity NPC198344
0.7156 Intermediate Similarity NPC188785
0.7155 Intermediate Similarity NPC103391
0.7155 Intermediate Similarity NPC472536
0.7132 Intermediate Similarity NPC471264
0.7132 Intermediate Similarity NPC471265
0.708 Intermediate Similarity NPC67009
0.7009 Intermediate Similarity NPC469739
0.6952 Remote Similarity NPC477538
0.6952 Remote Similarity NPC476019
0.694 Remote Similarity NPC209509
0.693 Remote Similarity NPC207820
0.69 Remote Similarity NPC246005
0.6869 Remote Similarity NPC476156
0.6869 Remote Similarity NPC476117
0.6869 Remote Similarity NPC476137
0.6869 Remote Similarity NPC476243
0.6842 Remote Similarity NPC263493
0.6842 Remote Similarity NPC269398
0.6814 Remote Similarity NPC205176
0.68 Remote Similarity NPC476302
0.68 Remote Similarity NPC470783
0.6788 Remote Similarity NPC240848
0.6771 Remote Similarity NPC178919
0.6768 Remote Similarity NPC31756
0.6733 Remote Similarity NPC184473
0.672 Remote Similarity NPC309525
0.6691 Remote Similarity NPC5620
0.6667 Remote Similarity NPC473741
0.6667 Remote Similarity NPC477145
0.6639 Remote Similarity NPC63191
0.6639 Remote Similarity NPC471202
0.6634 Remote Similarity NPC475542
0.6613 Remote Similarity NPC273185
0.6604 Remote Similarity NPC322966
0.6598 Remote Similarity NPC263281
0.6598 Remote Similarity NPC209156
0.6569 Remote Similarity NPC53858
0.6569 Remote Similarity NPC84128
0.6569 Remote Similarity NPC284456
0.6569 Remote Similarity NPC6902
0.6547 Remote Similarity NPC471820
0.6547 Remote Similarity NPC471821
0.6525 Remote Similarity NPC162104
0.6525 Remote Similarity NPC251122
0.6514 Remote Similarity NPC38172
0.6509 Remote Similarity NPC473495
0.6504 Remote Similarity NPC469899
0.65 Remote Similarity NPC129666
0.6475 Remote Similarity NPC329761
0.6475 Remote Similarity NPC225648
0.6449 Remote Similarity NPC155230
0.6436 Remote Similarity NPC312315
0.6429 Remote Similarity NPC266888
0.6429 Remote Similarity NPC256312
0.6429 Remote Similarity NPC161774
0.6423 Remote Similarity NPC139326
0.6421 Remote Similarity NPC10716
0.6392 Remote Similarity NPC196007
0.6392 Remote Similarity NPC76297
0.6392 Remote Similarity NPC214532
0.637 Remote Similarity NPC68865
0.6357 Remote Similarity NPC145113
0.6355 Remote Similarity NPC324506
0.6354 Remote Similarity NPC212866
0.6354 Remote Similarity NPC29598
0.6339 Remote Similarity NPC134504
0.6339 Remote Similarity NPC47076
0.6336 Remote Similarity NPC120335
0.6325 Remote Similarity NPC241394
0.6321 Remote Similarity NPC477539
0.632 Remote Similarity NPC470652
0.6301 Remote Similarity NPC197743
0.6301 Remote Similarity NPC297145
0.6296 Remote Similarity NPC275715
0.6293 Remote Similarity NPC265094
0.6286 Remote Similarity NPC262077
0.6273 Remote Similarity NPC315237
0.6271 Remote Similarity NPC271562
0.6263 Remote Similarity NPC126186
0.626 Remote Similarity NPC296043
0.626 Remote Similarity NPC473819
0.6259 Remote Similarity NPC476978
0.6259 Remote Similarity NPC52748
0.625 Remote Similarity NPC470653
0.625 Remote Similarity NPC470650
0.625 Remote Similarity NPC470654
0.6239 Remote Similarity NPC128303
0.6238 Remote Similarity NPC59867
0.6222 Remote Similarity NPC248283
0.6218 Remote Similarity NPC15413
0.6214 Remote Similarity NPC313867
0.6214 Remote Similarity NPC316008
0.621 Remote Similarity NPC329216
0.62 Remote Similarity NPC327272
0.6187 Remote Similarity NPC161069
0.617 Remote Similarity NPC314358
0.6159 Remote Similarity NPC268841
0.6159 Remote Similarity NPC239762
0.6159 Remote Similarity NPC163392
0.6159 Remote Similarity NPC307357
0.6159 Remote Similarity NPC46098
0.6143 Remote Similarity NPC314388
0.6143 Remote Similarity NPC315283
0.6142 Remote Similarity NPC477238
0.6142 Remote Similarity NPC160688
0.6139 Remote Similarity NPC470782
0.6131 Remote Similarity NPC127741
0.6122 Remote Similarity NPC478256
0.6099 Remote Similarity NPC315266
0.6084 Remote Similarity NPC105717
0.6077 Remote Similarity NPC6975
0.6068 Remote Similarity NPC471258
0.6042 Remote Similarity NPC2501
0.6034 Remote Similarity NPC233932
0.6017 Remote Similarity NPC471260
0.6014 Remote Similarity NPC138775
0.6 Remote Similarity NPC252878
0.6 Remote Similarity NPC36254
0.6 Remote Similarity NPC168113
0.5985 Remote Similarity NPC470651
0.5985 Remote Similarity NPC470655
0.5984 Remote Similarity NPC477237
0.5981 Remote Similarity NPC472351
0.5971 Remote Similarity NPC315210
0.5971 Remote Similarity NPC315848
0.5969 Remote Similarity NPC200964
0.5966 Remote Similarity NPC64168
0.5957 Remote Similarity NPC197682
0.5957 Remote Similarity NPC176226
0.5954 Remote Similarity NPC46427
0.595 Remote Similarity NPC474099
0.5935 Remote Similarity NPC30911
0.5935 Remote Similarity NPC316984
0.5932 Remote Similarity NPC474244
0.5923 Remote Similarity NPC202521
0.5923 Remote Similarity NPC50520
0.5918 Remote Similarity NPC286551
0.5918 Remote Similarity NPC122590
0.5917 Remote Similarity NPC471259
0.5912 Remote Similarity NPC287401
0.59 Remote Similarity NPC470781
0.589 Remote Similarity NPC7817
0.589 Remote Similarity NPC475168
0.5888 Remote Similarity NPC474312
0.5888 Remote Similarity NPC235078
0.5887 Remote Similarity NPC314550
0.5887 Remote Similarity NPC469427
0.5887 Remote Similarity NPC469426
0.5882 Remote Similarity NPC80439
0.5882 Remote Similarity NPC6271
0.5882 Remote Similarity NPC130309
0.5882 Remote Similarity NPC173690
0.5882 Remote Similarity NPC279833
0.5876 Remote Similarity NPC84182
0.5876 Remote Similarity NPC128005
0.5874 Remote Similarity NPC201244
0.5874 Remote Similarity NPC322878
0.5874 Remote Similarity NPC477217
0.5859 Remote Similarity NPC470788
0.5859 Remote Similarity NPC322274
0.5859 Remote Similarity NPC474812
0.5859 Remote Similarity NPC471261
0.5846 Remote Similarity NPC476990
0.5845 Remote Similarity NPC142761
0.5842 Remote Similarity NPC141325
0.584 Remote Similarity NPC193471
0.584 Remote Similarity NPC130124
0.5839 Remote Similarity NPC246079
0.5833 Remote Similarity NPC474371
0.5827 Remote Similarity NPC209734

  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 NPC475149 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
0.68 Remote Similarity NPD7762 Phase 2
0.68 Remote Similarity NPD7763 Phase 2
0.6796 Remote Similarity NPD7759 Phase 2
0.6796 Remote Similarity NPD7760 Phase 2
0.6792 Remote Similarity NPD4261 Phase 1
0.6792 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6727 Remote Similarity NPD8038 Phase 2
0.6579 Remote Similarity NPD6122 Discontinued
0.6509 Remote Similarity NPD3177 Phase 3
0.6476 Remote Similarity NPD3723 Clinical (unspecified phase)
0.641 Remote Similarity NPD2147 Approved
0.6408 Remote Similarity NPD2683 Discontinued
0.6396 Remote Similarity NPD7841 Clinical (unspecified phase)
0.6354 Remote Similarity NPD7840 Approved
0.6283 Remote Similarity NPD3713 Approved
0.6283 Remote Similarity NPD3714 Approved
0.6283 Remote Similarity NPD3715 Approved
0.625 Remote Similarity NPD1125 Discovery
0.6216 Remote Similarity NPD5781 Clinical (unspecified phase)
0.6202 Remote Similarity NPD2584 Suspended
0.6176 Remote Similarity NPD7113 Clinical (unspecified phase)
0.6131 Remote Similarity NPD8173 Phase 2
0.6131 Remote Similarity NPD8172 Phase 2
0.5935 Remote Similarity NPD2204 Approved
0.5897 Remote Similarity NPD6120 Clinical (unspecified phase)
0.5842 Remote Similarity NPD266 Phase 3
0.5842 Remote Similarity NPD265 Phase 3
0.5833 Remote Similarity NPD3733 Clinical (unspecified phase)
0.5833 Remote Similarity NPD9577 Approved
0.5821 Remote Similarity NPD2585 Clinical (unspecified phase)
0.58 Remote Similarity NPD2220 Clinical (unspecified phase)
0.5793 Remote Similarity NPD2054 Approved
0.5793 Remote Similarity NPD2055 Phase 3
0.5785 Remote Similarity NPD1385 Discontinued
0.5785 Remote Similarity NPD1428 Phase 2
0.5781 Remote Similarity NPD1773 Discontinued
0.5752 Remote Similarity NPD6095 Approved
0.5752 Remote Similarity NPD2682 Approved
0.5752 Remote Similarity NPD6094 Approved
0.5738 Remote Similarity NPD6937 Approved
0.5735 Remote Similarity NPD4177 Approved
0.5735 Remote Similarity NPD4175 Approved
0.5726 Remote Similarity NPD1805 Phase 2
0.5726 Remote Similarity NPD1804 Phase 2
0.5714 Remote Similarity NPD5767 Discontinued
0.5702 Remote Similarity NPD6699 Clinical (unspecified phase)
0.57 Remote Similarity NPD620 Approved
0.5692 Remote Similarity NPD2645 Approved
0.5674 Remote Similarity NPD6073 Approved
0.5674 Remote Similarity NPD5725 Approved
0.5669 Remote Similarity NPD1000 Clinical (unspecified phase)
0.5662 Remote Similarity NPD5339 Clinical (unspecified phase)
0.5659 Remote Similarity NPD2099 Approved
0.5644 Remote Similarity NPD9649 Approved
0.5643 Remote Similarity NPD8416 Discontinued
0.5638 Remote Similarity NPD7613 Discontinued
0.5615 Remote Similarity NPD3159 Discontinued
0.5612 Remote Similarity NPD8415 Approved
0.5606 Remote Similarity NPD1748 Approved
0.5606 Remote Similarity NPD1806 Approved
0.56 Remote Similarity NPD6421 Discontinued

  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