NPASS Compound

Structure

NPC473595 OpenBabel07101718192D 45 48 0 0 1 0 0 0 0 0999 V2000 3.2041 -1.8436 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2874 2.8673 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5074 0.1156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6967 6.1088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2041 4.0340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8364 5.8370 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1120 -1.8922 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0036 1.8366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7786 -1.4669 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3558 -1.3538 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3558 -0.3742 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7800 3.3571 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3558 1.5850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3558 2.5646 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3558 2.5646 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5074 1.0952 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6967 5.1292 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3558 4.5238 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2606 5.0445 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1378 -1.7898 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3558 1.5850 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8484 3.6598 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5074 3.0544 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7800 0.7925 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2041 0.1156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6591 1.5850 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0833 3.3571 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0833 0.7925 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7800 -0.7925 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6591 2.5646 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8484 -0.4898 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8484 0.4898 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5451 4.6394 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3558 5.5034 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7136 5.1469 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4380 -2.5823 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0525 -0.3742 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0827 -1.7242 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8484 4.6394 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5074 4.0340 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6591 4.1496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6591 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2041 1.0952 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3558 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 1 0 0 0 0 2 15 1 0 0 0 0 4 17 1 0 0 0 0 5 18 1 0 0 0 0 6 19 1 0 0 0 0 7 20 1 0 0 0 0 9 31 1 0 0 0 0 10 11 1 0 0 0 0 11 25 1 0 0 0 0 12 15 1 0 0 0 0 12 22 1 0 0 0 0 13 15 2 0 0 0 0 13 24 1 0 0 0 0 14 21 1 0 0 0 0 14 23 1 0 0 0 0 16 3 1 6 0 0 0 16 21 1 0 0 0 0 16 26 1 0 0 0 0 17 33 2 0 0 0 0 17 39 1 0 0 0 0 18 34 2 0 0 0 0 18 40 1 0 0 0 0 19 35 2 0 0 0 0 19 41 1 0 0 0 0 20 36 2 0 0 0 0 20 42 1 0 0 0 0 21 43 1 6 0 0 0 22 27 1 0 0 0 0 22 39 1 6 0 0 0 23 30 1 1 0 0 0 23 40 1 0 0 0 0 24 32 1 1 0 0 0 24 44 1 0 0 0 0 25 37 2 0 0 0 0 25 43 1 0 0 0 0 26 28 1 0 0 0 0 26 30 1 6 0 0 0 27 30 1 1 0 0 0 27 41 1 0 0 0 0 28 32 1 1 0 0 0 28 42 1 0 0 0 0 29 31 1 0 0 0 0 29 38 2 0 0 0 0 29 44 1 0 0 0 0 30 8 1 6 0 0 0 31 32 1 6 0 0 0 31 45 1 0 0 0 0 32 45 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	636.28
Volume:	623.62
LogP:	3.266
LogD:	2.158
LogS:	-4.579
# Rotatable Bonds:	12
TPSA:	170.33
# H-Bond Aceptor:	13
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.173
Synthetic Accessibility Score:	6.224
Fsp3:	0.75
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:	-5.098
MDCK Permeability:	0.00015809238539077342
Pgp-inhibitor:	1.0
Pgp-substrate:	0.044
Human Intestinal Absorption (HIA):	0.709
20% Bioavailability (F20%):	0.012
30% Bioavailability (F30%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.321
Plasma Protein Binding (PPB):	60.42910385131836%
Volume Distribution (VD):	1.665
Pgp-substrate:	30.464771270751953%

ADMET: Metabolism

CYP1A2-inhibitor:	0.008
CYP1A2-substrate:	0.011
CYP2C19-inhibitor:	0.012
CYP2C19-substrate:	0.104
CYP2C9-inhibitor:	0.005
CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.374
CYP2D6-substrate:	0.047
CYP3A4-inhibitor:	0.396
CYP3A4-substrate:	0.44

ADMET: Excretion

Clearance (CL):	3.749
Half-life (T1/2):	0.796

ADMET: Toxicity

hERG Blockers:	0.054
Human Hepatotoxicity (H-HT):	0.958
Drug-inuced Liver Injury (DILI):	0.97
AMES Toxicity:	0.065
Rat Oral Acute Toxicity:	0.567
Maximum Recommended Daily Dose:	0.032
Skin Sensitization:	0.611
Carcinogencity:	0.102
Eye Corrosion:	0.751
Eye Irritation:	0.147
Respiratory Toxicity:	0.673

Download Data

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

Natural Product: NPC473595

Natural Product ID:	NPC473595
*Common Name:**	Excavatolide J
IUPAC Name:	n.a.
Synonyms:	Excavatolide J
Standard InCHIKey:	RDDNEKXKTMRLDN-HLYBBLBISA-N
Standard InCHI:	InChI=1S/C32H44O13/c1-10-11-25(37)43-21-14-23(40-18(5)34)30(8)26(16(21)3)28(42-20(7)36)32-24(44-29(38)31(32,9)45-32)13-15(2)12-22(39-17(4)33)27(30)41-19(6)35/h13,16,21-24,26-28H,10-12,14H2,1-9H3/b15-13-/t16-,21-,22-,23-,24-,26+,27+,28+,30-,31-,32-/m0/s1
SMILES:	CCCC(=O)O[C@H]1C[C@H](OC(=O)C)[C@]2([C@H]([C@H]1C)[C@@H](OC(=O)C)[C@@]13O[C@@]3(C)C(=O)O[C@H]1/C=C(C[C@@H]([C@H]2OC(=O)C)OC(=O)C)/C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL446830
PubChem CID:	10675560
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

*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
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10096858]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10543904]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11277747]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11720523]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9599257]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	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

Activity Type	# Activity
ED50	4

Activity Type	# Activity
Cell Line	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	ED50	=	3.8	ug ml-1	PMID[524087]
NPT91	Cell Line	KB	Homo sapiens	ED50	=	6.5	ug ml-1	PMID[524087]
NPT81	Cell Line	A549	Homo sapiens	ED50	=	5.2	ug ml-1	PMID[524087]
NPT139	Cell Line	HT-29	Homo sapiens	ED50	=	5.2	ug ml-1	PMID[524087]

☑ 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 NPC473595 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	266
0.1-0.2	1576
0.2-0.3	4905
0.3-0.4	8912
0.4-0.5	13399
0.5-0.6	7352
0.6-0.7	5125
0.7-0.8	1077
0.8-0.85	44
0.85-0.9	21
0.9-0.95	12
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC473939
0.9899	High Similarity	NPC475587
0.9899	High Similarity	NPC475510
0.9608	High Similarity	NPC473843
0.9608	High Similarity	NPC473975
0.9608	High Similarity	NPC473594
0.9608	High Similarity	NPC474586
0.9608	High Similarity	NPC281624
0.9515	High Similarity	NPC194619
0.9423	High Similarity	NPC473877
0.94	High Similarity	NPC19239
0.94	High Similarity	NPC474166
0.9159	High Similarity	NPC474333
0.9135	High Similarity	NPC42662
0.9074	High Similarity	NPC296822
0.9038	High Similarity	NPC94377
0.8952	High Similarity	NPC475922
0.8889	High Similarity	NPC73314
0.8868	High Similarity	NPC161816
0.8868	High Similarity	NPC115257
0.8807	High Similarity	NPC476710
0.8807	High Similarity	NPC476711
0.8727	High Similarity	NPC476713
0.8727	High Similarity	NPC476712
0.8679	High Similarity	NPC169888
0.8679	High Similarity	NPC327286
0.8679	High Similarity	NPC55972
0.8667	High Similarity	NPC9303
0.8667	High Similarity	NPC16313
0.8667	High Similarity	NPC475802
0.8598	High Similarity	NPC15218
0.8585	High Similarity	NPC474421
0.8585	High Similarity	NPC326994
0.8585	High Similarity	NPC72813
0.8585	High Similarity	NPC194620
0.8585	High Similarity	NPC324327
0.8571	High Similarity	NPC470186
0.8558	High Similarity	NPC183571
0.8505	High Similarity	NPC233379
0.8505	High Similarity	NPC14862
0.8505	High Similarity	NPC474664
0.8476	Intermediate Similarity	NPC474165
0.8476	Intermediate Similarity	NPC69171
0.8468	Intermediate Similarity	NPC477509
0.8455	Intermediate Similarity	NPC477126
0.8396	Intermediate Similarity	NPC477127
0.8364	Intermediate Similarity	NPC471933
0.835	Intermediate Similarity	NPC471140
0.8304	Intermediate Similarity	NPC270478
0.8302	Intermediate Similarity	NPC4620
0.8286	Intermediate Similarity	NPC476478
0.8276	Intermediate Similarity	NPC303006
0.8241	Intermediate Similarity	NPC474716
0.8224	Intermediate Similarity	NPC220964
0.8224	Intermediate Similarity	NPC475676
0.8198	Intermediate Similarity	NPC317687
0.819	Intermediate Similarity	NPC188222
0.819	Intermediate Similarity	NPC282003
0.819	Intermediate Similarity	NPC310035
0.8148	Intermediate Similarity	NPC470979
0.8148	Intermediate Similarity	NPC470975
0.8148	Intermediate Similarity	NPC103088
0.8113	Intermediate Similarity	NPC477511
0.8113	Intermediate Similarity	NPC98225
0.8113	Intermediate Similarity	NPC264477
0.8108	Intermediate Similarity	NPC317107
0.8099	Intermediate Similarity	NPC470185
0.8095	Intermediate Similarity	NPC264378
0.8091	Intermediate Similarity	NPC471934
0.8091	Intermediate Similarity	NPC469370
0.8077	Intermediate Similarity	NPC17585
0.8073	Intermediate Similarity	NPC180744
0.807	Intermediate Similarity	NPC473590
0.8058	Intermediate Similarity	NPC161998
0.802	Intermediate Similarity	NPC475971
0.8018	Intermediate Similarity	NPC472215
0.8018	Intermediate Similarity	NPC475563
0.8018	Intermediate Similarity	NPC253906
0.8018	Intermediate Similarity	NPC472214
0.8018	Intermediate Similarity	NPC475134
0.8017	Intermediate Similarity	NPC475003
0.8	Intermediate Similarity	NPC322903
0.7966	Intermediate Similarity	NPC67251
0.7946	Intermediate Similarity	NPC475668
0.7946	Intermediate Similarity	NPC473921
0.7946	Intermediate Similarity	NPC475480
0.7944	Intermediate Similarity	NPC164598
0.7944	Intermediate Similarity	NPC474339
0.7913	Intermediate Similarity	NPC469684
0.7909	Intermediate Similarity	NPC469558
0.7895	Intermediate Similarity	NPC226608
0.7895	Intermediate Similarity	NPC88867
0.789	Intermediate Similarity	NPC471143
0.789	Intermediate Similarity	NPC477510
0.7876	Intermediate Similarity	NPC470468
0.787	Intermediate Similarity	NPC474709
0.787	Intermediate Similarity	NPC471148
0.785	Intermediate Similarity	NPC477512
0.785	Intermediate Similarity	NPC469551
0.7845	Intermediate Similarity	NPC470776
0.7838	Intermediate Similarity	NPC476479
0.783	Intermediate Similarity	NPC100912
0.7826	Intermediate Similarity	NPC470466
0.7826	Intermediate Similarity	NPC474734
0.7826	Intermediate Similarity	NPC470793
0.7822	Intermediate Similarity	NPC266957
0.7818	Intermediate Similarity	NPC284365
0.7818	Intermediate Similarity	NPC123726
0.7815	Intermediate Similarity	NPC91693
0.7815	Intermediate Similarity	NPC472399
0.7815	Intermediate Similarity	NPC18945
0.7815	Intermediate Similarity	NPC105926
0.7815	Intermediate Similarity	NPC265557
0.7815	Intermediate Similarity	NPC473802
0.7807	Intermediate Similarity	NPC470120
0.7807	Intermediate Similarity	NPC159333
0.7807	Intermediate Similarity	NPC89018
0.7807	Intermediate Similarity	NPC33360
0.7797	Intermediate Similarity	NPC470779
0.7797	Intermediate Similarity	NPC52839
0.7788	Intermediate Similarity	NPC476598
0.7788	Intermediate Similarity	NPC474846
0.7788	Intermediate Similarity	NPC470467
0.7788	Intermediate Similarity	NPC469655
0.7788	Intermediate Similarity	NPC476597
0.7788	Intermediate Similarity	NPC469656
0.7778	Intermediate Similarity	NPC475520
0.7768	Intermediate Similarity	NPC475191
0.7767	Intermediate Similarity	NPC475748
0.7759	Intermediate Similarity	NPC176513
0.7759	Intermediate Similarity	NPC470775
0.7759	Intermediate Similarity	NPC98249
0.7759	Intermediate Similarity	NPC58662
0.7759	Intermediate Similarity	NPC53396
0.7757	Intermediate Similarity	NPC72647
0.7757	Intermediate Similarity	NPC107806
0.775	Intermediate Similarity	NPC476729
0.775	Intermediate Similarity	NPC473709
0.775	Intermediate Similarity	NPC24651
0.775	Intermediate Similarity	NPC473919
0.7748	Intermediate Similarity	NPC477513
0.7748	Intermediate Similarity	NPC67321
0.7748	Intermediate Similarity	NPC187435
0.7731	Intermediate Similarity	NPC19464
0.7731	Intermediate Similarity	NPC312833
0.7731	Intermediate Similarity	NPC162009
0.7731	Intermediate Similarity	NPC257017
0.7727	Intermediate Similarity	NPC258532
0.7727	Intermediate Similarity	NPC146731
0.7723	Intermediate Similarity	NPC50637
0.7719	Intermediate Similarity	NPC269530
0.7719	Intermediate Similarity	NPC473522
0.7719	Intermediate Similarity	NPC475277
0.7719	Intermediate Similarity	NPC477093
0.7719	Intermediate Similarity	NPC222834
0.7714	Intermediate Similarity	NPC471147
0.7714	Intermediate Similarity	NPC476596
0.7712	Intermediate Similarity	NPC4548
0.7712	Intermediate Similarity	NPC471126
0.7712	Intermediate Similarity	NPC471128
0.7712	Intermediate Similarity	NPC145182
0.7712	Intermediate Similarity	NPC157252
0.7706	Intermediate Similarity	NPC476081
0.7706	Intermediate Similarity	NPC105725
0.7705	Intermediate Similarity	NPC236999
0.7692	Intermediate Similarity	NPC207641
0.7692	Intermediate Similarity	NPC20713
0.7692	Intermediate Similarity	NPC284707
0.7692	Intermediate Similarity	NPC49420
0.7692	Intermediate Similarity	NPC233437
0.7692	Intermediate Similarity	NPC473720
0.7686	Intermediate Similarity	NPC471939
0.7686	Intermediate Similarity	NPC181999
0.7686	Intermediate Similarity	NPC473635
0.7685	Intermediate Similarity	NPC474718
0.7685	Intermediate Similarity	NPC475949
0.767	Intermediate Similarity	NPC151770
0.7664	Intermediate Similarity	NPC475446
0.7664	Intermediate Similarity	NPC474921
0.7664	Intermediate Similarity	NPC311241
0.7658	Intermediate Similarity	NPC475414
0.7658	Intermediate Similarity	NPC173172
0.7652	Intermediate Similarity	NPC474937
0.7652	Intermediate Similarity	NPC94509
0.7652	Intermediate Similarity	NPC473535
0.7647	Intermediate Similarity	NPC472401
0.7642	Intermediate Similarity	NPC475659
0.7642	Intermediate Similarity	NPC476851
0.7632	Intermediate Similarity	NPC170294
0.7632	Intermediate Similarity	NPC475495
0.7632	Intermediate Similarity	NPC157476
0.7627	Intermediate Similarity	NPC471108
0.7627	Intermediate Similarity	NPC275696
0.7627	Intermediate Similarity	NPC5991
0.7627	Intermediate Similarity	NPC312536
0.7627	Intermediate Similarity	NPC472667
0.7627	Intermediate Similarity	NPC22628
0.7627	Intermediate Similarity	NPC255081
0.7627	Intermediate Similarity	NPC5989
0.7623	Intermediate Similarity	NPC470780

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 NPC473595 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	225
0.1-0.2	2002
0.2-0.3	3830
0.3-0.4	2022
0.4-0.5	669
0.5-0.6	273
0.6-0.7	122
0.7-0.8	7
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7589	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.7434	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.7391	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7282	Intermediate Similarity	NPD1733	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD4225	Approved
0.7217	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7167	Intermediate Similarity	NPD7115	Discovery
0.7155	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7103	Intermediate Similarity	NPD6698	Approved
0.7103	Intermediate Similarity	NPD46	Approved
0.7054	Intermediate Similarity	NPD6648	Approved
0.7043	Intermediate Similarity	NPD6008	Approved
0.6991	Remote Similarity	NPD5344	Discontinued
0.6949	Remote Similarity	NPD6371	Approved
0.6923	Remote Similarity	NPD6686	Approved
0.6891	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6885	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6855	Remote Similarity	NPD6319	Approved
0.6852	Remote Similarity	NPD1695	Approved
0.6833	Remote Similarity	NPD8297	Approved
0.6825	Remote Similarity	NPD8328	Phase 3
0.6822	Remote Similarity	NPD7319	Approved
0.6814	Remote Similarity	NPD7638	Approved
0.68	Remote Similarity	NPD8515	Approved
0.68	Remote Similarity	NPD8517	Approved
0.68	Remote Similarity	NPD8516	Approved
0.68	Remote Similarity	NPD8513	Phase 3
0.6797	Remote Similarity	NPD8293	Discontinued
0.6772	Remote Similarity	NPD7492	Approved
0.6757	Remote Similarity	NPD5282	Discontinued
0.6754	Remote Similarity	NPD7640	Approved
0.6754	Remote Similarity	NPD7639	Approved
0.6744	Remote Similarity	NPD7736	Approved
0.6727	Remote Similarity	NPD7983	Approved
0.6723	Remote Similarity	NPD6373	Approved
0.6723	Remote Similarity	NPD6372	Approved
0.672	Remote Similarity	NPD6054	Approved
0.672	Remote Similarity	NPD6059	Approved
0.6719	Remote Similarity	NPD6616	Approved
0.6667	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD7078	Approved
0.6667	Remote Similarity	NPD6921	Approved
0.6636	Remote Similarity	NPD7838	Discovery
0.6636	Remote Similarity	NPD1694	Approved
0.6614	Remote Similarity	NPD6370	Approved
0.6612	Remote Similarity	NPD6649	Approved
0.6612	Remote Similarity	NPD6650	Approved
0.661	Remote Similarity	NPD6675	Approved
0.661	Remote Similarity	NPD5739	Approved
0.661	Remote Similarity	NPD6402	Approved
0.661	Remote Similarity	NPD7128	Approved
0.6607	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6607	Remote Similarity	NPD7900	Approved
0.6589	Remote Similarity	NPD7507	Approved
0.6552	Remote Similarity	NPD1700	Approved
0.6538	Remote Similarity	NPD8074	Phase 3
0.6535	Remote Similarity	NPD6015	Approved
0.6535	Remote Similarity	NPD6016	Approved
0.6518	Remote Similarity	NPD5779	Approved
0.6518	Remote Similarity	NPD5778	Approved
0.6518	Remote Similarity	NPD6399	Phase 3
0.6504	Remote Similarity	NPD8133	Approved
0.65	Remote Similarity	NPD6899	Approved
0.65	Remote Similarity	NPD7320	Approved
0.65	Remote Similarity	NPD6881	Approved
0.6484	Remote Similarity	NPD5988	Approved
0.6475	Remote Similarity	NPD8130	Phase 1
0.6455	Remote Similarity	NPD6672	Approved
0.6455	Remote Similarity	NPD5737	Approved
0.6446	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6435	Remote Similarity	NPD7902	Approved
0.6434	Remote Similarity	NPD7604	Phase 2
0.6429	Remote Similarity	NPD7327	Approved
0.6429	Remote Similarity	NPD5693	Phase 1
0.6429	Remote Similarity	NPD7328	Approved
0.6429	Remote Similarity	NPD7637	Suspended
0.6423	Remote Similarity	NPD6882	Approved
0.6417	Remote Similarity	NPD5697	Approved
0.6417	Remote Similarity	NPD5701	Approved
0.6406	Remote Similarity	NPD8296	Approved
0.6406	Remote Similarity	NPD8378	Approved
0.6406	Remote Similarity	NPD8380	Approved
0.6406	Remote Similarity	NPD8335	Approved
0.6406	Remote Similarity	NPD8379	Approved
0.6406	Remote Similarity	NPD8033	Approved
0.6404	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6404	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6393	Remote Similarity	NPD7102	Approved
0.6393	Remote Similarity	NPD7290	Approved
0.6393	Remote Similarity	NPD6883	Approved
0.6378	Remote Similarity	NPD7516	Approved
0.6371	Remote Similarity	NPD4632	Approved
0.6349	Remote Similarity	NPD6009	Approved
0.6341	Remote Similarity	NPD6847	Approved
0.6341	Remote Similarity	NPD6617	Approved
0.6341	Remote Similarity	NPD6869	Approved
0.6328	Remote Similarity	NPD8377	Approved
0.6328	Remote Similarity	NPD8294	Approved
0.6316	Remote Similarity	NPD7748	Approved
0.6311	Remote Similarity	NPD8039	Approved
0.6311	Remote Similarity	NPD6013	Approved
0.6311	Remote Similarity	NPD6012	Approved
0.6311	Remote Similarity	NPD6014	Approved
0.6293	Remote Similarity	NPD6083	Phase 2
0.6293	Remote Similarity	NPD6084	Phase 2
0.6283	Remote Similarity	NPD8035	Phase 2
0.6283	Remote Similarity	NPD6411	Approved
0.6283	Remote Similarity	NPD8034	Phase 2
0.6279	Remote Similarity	NPD5983	Phase 2
0.6273	Remote Similarity	NPD6098	Approved
0.6261	Remote Similarity	NPD5695	Phase 3
0.625	Remote Similarity	NPD6673	Approved
0.625	Remote Similarity	NPD6904	Approved
0.625	Remote Similarity	NPD6080	Approved
0.6241	Remote Similarity	NPD6033	Approved
0.6239	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6239	Remote Similarity	NPD5696	Approved
0.6232	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.623	Remote Similarity	NPD6011	Approved
0.6222	Remote Similarity	NPD7260	Phase 2
0.6218	Remote Similarity	NPD7632	Discontinued
0.6212	Remote Similarity	NPD6336	Discontinued
0.621	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6195	Remote Similarity	NPD5785	Approved
0.6195	Remote Similarity	NPD3168	Discontinued
0.616	Remote Similarity	NPD6053	Discontinued
0.614	Remote Similarity	NPD6050	Approved
0.6129	Remote Similarity	NPD4634	Approved
0.6126	Remote Similarity	NPD7521	Approved
0.6126	Remote Similarity	NPD5330	Approved
0.6126	Remote Similarity	NPD7334	Approved
0.6126	Remote Similarity	NPD6409	Approved
0.6126	Remote Similarity	NPD6684	Approved
0.6126	Remote Similarity	NPD7146	Approved
0.6106	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6106	Remote Similarity	NPD6051	Approved
0.6106	Remote Similarity	NPD6101	Approved
0.609	Remote Similarity	NPD8273	Phase 1
0.6068	Remote Similarity	NPD7839	Suspended
0.6058	Remote Similarity	NPD6845	Suspended
0.6055	Remote Similarity	NPD5209	Approved
0.6053	Remote Similarity	NPD5692	Phase 3
0.6034	Remote Similarity	NPD6001	Approved
0.6031	Remote Similarity	NPD7503	Approved
0.6018	Remote Similarity	NPD6903	Approved
0.6018	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6017	Remote Similarity	NPD4755	Approved
0.6016	Remote Similarity	NPD6412	Phase 2
0.6016	Remote Similarity	NPD6274	Approved
0.6	Remote Similarity	NPD7101	Approved
0.6	Remote Similarity	NPD7100	Approved
0.6	Remote Similarity	NPD7515	Phase 2
0.6	Remote Similarity	NPD5694	Approved
0.5963	Remote Similarity	NPD5369	Approved
0.595	Remote Similarity	NPD3653	Clinical (unspecified phase)
0.595	Remote Similarity	NPD5211	Phase 2
0.5946	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.5929	Remote Similarity	NPD4250	Approved
0.5929	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5929	Remote Similarity	NPD3573	Approved
0.5929	Remote Similarity	NPD4251	Approved
0.5929	Remote Similarity	NPD7524	Approved
0.5923	Remote Similarity	NPD6335	Approved
0.5917	Remote Similarity	NPD4696	Approved
0.5917	Remote Similarity	NPD5286	Approved
0.5917	Remote Similarity	NPD5285	Approved
0.5917	Remote Similarity	NPD4700	Approved
0.5909	Remote Similarity	NPD4270	Approved
0.5909	Remote Similarity	NPD6909	Approved
0.5909	Remote Similarity	NPD4269	Approved
0.5909	Remote Similarity	NPD6908	Approved
0.5857	Remote Similarity	NPD8415	Approved
0.5856	Remote Similarity	NPD7154	Phase 3
0.5856	Remote Similarity	NPD6695	Phase 3
0.5854	Remote Similarity	NPD5141	Approved
0.5852	Remote Similarity	NPD8451	Approved
0.5846	Remote Similarity	NPD6317	Approved
0.5841	Remote Similarity	NPD3618	Phase 1
0.5841	Remote Similarity	NPD5786	Approved
0.5841	Remote Similarity	NPD4249	Approved
0.5821	Remote Similarity	NPD7642	Approved
0.5821	Remote Similarity	NPD7830	Approved
0.5821	Remote Similarity	NPD7829	Approved
0.582	Remote Similarity	NPD5225	Approved
0.582	Remote Similarity	NPD4633	Approved
0.582	Remote Similarity	NPD5226	Approved
0.582	Remote Similarity	NPD5224	Approved
0.5809	Remote Similarity	NPD8448	Approved
0.5806	Remote Similarity	NPD4767	Approved
0.5806	Remote Similarity	NPD4768	Approved
0.5804	Remote Similarity	NPD4786	Approved
0.5804	Remote Similarity	NPD3668	Phase 3
0.5802	Remote Similarity	NPD6313	Approved
0.5802	Remote Similarity	NPD6314	Approved
0.5798	Remote Similarity	NPD4697	Phase 3
0.5797	Remote Similarity	NPD5956	Approved
0.5789	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.5789	Remote Similarity	NPD7750	Discontinued
0.5776	Remote Similarity	NPD5207	Approved
0.5772	Remote Similarity	NPD5174	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