NPASS Compound

Structure

NPC469463 OpenBabel07101718202D 29 31 0 0 1 0 0 0 0 0999 V2000 6.9282 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0981 -0.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 3.5000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9511 0.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0622 4.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2601 1.2601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4067 0.9135 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5388 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 15 1 0 0 0 0 2 21 1 0 0 0 0 3 21 1 0 0 0 0 4 22 1 0 0 0 0 5 6 2 0 0 0 0 5 7 1 0 0 0 0 6 9 1 0 0 0 0 7 10 2 0 0 0 0 8 11 1 0 0 0 0 8 12 1 0 0 0 0 9 15 1 0 0 0 0 10 18 1 0 0 0 0 11 21 1 0 0 0 0 12 22 1 0 0 0 0 13 16 2 0 0 0 0 13 17 1 0 0 0 0 14 16 1 0 0 0 0 14 28 1 0 0 0 0 15 24 1 0 0 0 0 16 23 1 0 0 0 0 17 19 1 0 0 0 0 17 29 1 6 0 0 0 18 25 2 0 0 0 0 18 29 1 0 0 0 0 19 21 1 0 0 0 0 19 22 1 6 0 0 0 20 23 1 0 0 0 0 20 26 2 0 0 0 0 20 28 1 0 0 0 0 22 23 1 1 0 0 0 23 27 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	404.22
Volume:	420.254
LogP:	3.256
LogD:	2.776
LogS:	-3.756
# Rotatable Bonds:	6
TPSA:	93.06
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.416
Synthetic Accessibility Score:	4.934
Fsp3:	0.652
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.701
MDCK Permeability:	2.7764937840402126e-05
Pgp-inhibitor:	0.912
Pgp-substrate:	0.012
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.01
30% Bioavailability (F30%):	0.933

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.783
Plasma Protein Binding (PPB):	69.27599334716797%
Volume Distribution (VD):	1.375
Pgp-substrate:	27.53753662109375%

ADMET: Metabolism

CYP1A2-inhibitor:	0.032
CYP1A2-substrate:	0.11
CYP2C19-inhibitor:	0.191
CYP2C19-substrate:	0.63
CYP2C9-inhibitor:	0.193
CYP2C9-substrate:	0.038
CYP2D6-inhibitor:	0.004
CYP2D6-substrate:	0.077
CYP3A4-inhibitor:	0.762
CYP3A4-substrate:	0.601

ADMET: Excretion

Clearance (CL):	5.709
Half-life (T1/2):	0.079

ADMET: Toxicity

hERG Blockers:	0.033
Human Hepatotoxicity (H-HT):	0.314
Drug-inuced Liver Injury (DILI):	0.806
AMES Toxicity:	0.943
Rat Oral Acute Toxicity:	0.917
Maximum Recommended Daily Dose:	0.936
Skin Sensitization:	0.355
Carcinogencity:	0.958
Eye Corrosion:	0.004
Eye Irritation:	0.012
Respiratory Toxicity:	0.966

Download Data

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

Natural Product: NPC469463

Natural Product ID:	NPC469463
*Common Name:**	Ustusolate C
IUPAC Name:	[(5R,5aS,9aS,9bS)-9b-hydroxy-6,6,9a-trimethyl-1-oxo-3,5,5a,7,8,9-hexahydrobenzo[e][2]benzofuran-5-yl] (2E,4E)-7-hydroxyocta-2,4-dienoate
Synonyms:	Ustusolate C
Standard InCHIKey:	GWQSYRUODDDVOT-WMQXXUAISA-N
Standard InCHI:	InChI=1S/C23H32O6/c1-15(24)9-6-5-7-10-18(25)29-17-13-16-14-28-20(26)23(16,27)22(4)12-8-11-21(2,3)19(17)22/h5-7,10,13,15,17,19,24,27H,8-9,11-12,14H2,1-4H3/b6-5+,10-7+/t15?,17-,19+,22+,23+/m1/s1
SMILES:	CC(C/C=C/C=C/C(=O)O[C@@H]1C=C2COC(=O)[C@@]2([C@@]2([C@@H]1C(C)(C)CCC2)C)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1079307
PubChem CID:	44557565
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001634] Naphthofurans

*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
NPO27058	Aspergillus ustus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19769341]
NPO27058	Aspergillus ustus	Species	Aspergillaceae	Eukaryota	Suberites domuncula	n.a.	n.a.	PMID[19778087]
NPO27058	Aspergillus ustus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21348461]
NPO27058	Aspergillus ustus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24033077]
NPO27058	Aspergillus ustus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25706180]
NPO27058	Aspergillus ustus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29286660]
NPO27058	Aspergillus ustus	Species	Aspergillaceae	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
IC50	2

Activity Type	# Activity
Cell Line	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	IC50	=	10500.0	nM	PMID[506502]
NPT116	Cell Line	HL-60	Homo sapiens	IC50	>	100000.0	nM	PMID[506502]

☑ 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 NPC469463 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	197
0.1-0.2	948
0.2-0.3	3286
0.3-0.4	6379
0.4-0.5	12531
0.5-0.6	9030
0.6-0.7	6882
0.7-0.8	3225
0.8-0.85	185
0.85-0.9	24
0.9-0.95	2
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC469496
1.0	High Similarity	NPC469454
0.9808	High Similarity	NPC304180
0.9808	High Similarity	NPC179798
0.9712	High Similarity	NPC5103
0.9623	High Similarity	NPC56448
0.9537	High Similarity	NPC23046
0.9231	High Similarity	NPC258532
0.9143	High Similarity	NPC477125
0.8868	High Similarity	NPC146731
0.8868	High Similarity	NPC296950
0.8818	High Similarity	NPC269530
0.8636	High Similarity	NPC235014
0.8611	High Similarity	NPC469607
0.8596	High Similarity	NPC284707
0.8571	High Similarity	NPC23364
0.8571	High Similarity	NPC25909
0.8571	High Similarity	NPC471204
0.8559	High Similarity	NPC188738
0.8547	High Similarity	NPC67251
0.8532	High Similarity	NPC187435
0.8532	High Similarity	NPC67321
0.8522	High Similarity	NPC476529
0.8522	High Similarity	NPC475775
0.8509	High Similarity	NPC473590
0.8509	High Similarity	NPC473968
0.8509	High Similarity	NPC53396
0.8509	High Similarity	NPC469684
0.8509	High Similarity	NPC98249
0.8505	High Similarity	NPC235369
0.8505	High Similarity	NPC295791
0.8496	Intermediate Similarity	NPC474181
0.8482	Intermediate Similarity	NPC236217
0.8482	Intermediate Similarity	NPC476801
0.8475	Intermediate Similarity	NPC470922
0.8468	Intermediate Similarity	NPC478211
0.8468	Intermediate Similarity	NPC210005
0.8455	Intermediate Similarity	NPC476479
0.8455	Intermediate Similarity	NPC189075
0.8455	Intermediate Similarity	NPC275539
0.8448	Intermediate Similarity	NPC107338
0.8448	Intermediate Similarity	NPC475885
0.8448	Intermediate Similarity	NPC109607
0.8421	Intermediate Similarity	NPC474734
0.8421	Intermediate Similarity	NPC179626
0.8421	Intermediate Similarity	NPC176840
0.8421	Intermediate Similarity	NPC478216
0.8407	Intermediate Similarity	NPC474271
0.8393	Intermediate Similarity	NPC132790
0.8393	Intermediate Similarity	NPC317107
0.8393	Intermediate Similarity	NPC100329
0.8393	Intermediate Similarity	NPC247031
0.8393	Intermediate Similarity	NPC97939
0.839	Intermediate Similarity	NPC469789
0.8378	Intermediate Similarity	NPC141350
0.8376	Intermediate Similarity	NPC46570
0.8365	Intermediate Similarity	NPC469491
0.8364	Intermediate Similarity	NPC144854
0.8364	Intermediate Similarity	NPC3316
0.8364	Intermediate Similarity	NPC110496
0.8362	Intermediate Similarity	NPC236918
0.8362	Intermediate Similarity	NPC156745
0.8362	Intermediate Similarity	NPC270850
0.8362	Intermediate Similarity	NPC305260
0.8349	Intermediate Similarity	NPC475676
0.8349	Intermediate Similarity	NPC220964
0.8333	Intermediate Similarity	NPC31058
0.8333	Intermediate Similarity	NPC265290
0.8333	Intermediate Similarity	NPC469606
0.8333	Intermediate Similarity	NPC305044
0.8333	Intermediate Similarity	NPC473596
0.8333	Intermediate Similarity	NPC273005
0.8319	Intermediate Similarity	NPC317687
0.8319	Intermediate Similarity	NPC8369
0.8319	Intermediate Similarity	NPC126691
0.8319	Intermediate Similarity	NPC472002
0.8319	Intermediate Similarity	NPC476729
0.8319	Intermediate Similarity	NPC145238
0.8319	Intermediate Similarity	NPC24651
0.8305	Intermediate Similarity	NPC107493
0.8304	Intermediate Similarity	NPC286880
0.8304	Intermediate Similarity	NPC37116
0.8291	Intermediate Similarity	NPC474585
0.8291	Intermediate Similarity	NPC79579
0.8291	Intermediate Similarity	NPC19336
0.8291	Intermediate Similarity	NPC185876
0.8291	Intermediate Similarity	NPC48692
0.8291	Intermediate Similarity	NPC329080
0.8291	Intermediate Similarity	NPC472759
0.8288	Intermediate Similarity	NPC476802
0.8288	Intermediate Similarity	NPC89171
0.8288	Intermediate Similarity	NPC306265
0.8288	Intermediate Similarity	NPC154608
0.8288	Intermediate Similarity	NPC192813
0.8288	Intermediate Similarity	NPC277017
0.8286	Intermediate Similarity	NPC36954
0.8276	Intermediate Similarity	NPC472760
0.8276	Intermediate Similarity	NPC153440
0.8276	Intermediate Similarity	NPC21326
0.8273	Intermediate Similarity	NPC472751
0.8273	Intermediate Similarity	NPC472749
0.8269	Intermediate Similarity	NPC475912
0.8264	Intermediate Similarity	NPC236999
0.8261	Intermediate Similarity	NPC474046
0.8261	Intermediate Similarity	NPC96312
0.8261	Intermediate Similarity	NPC328374
0.8261	Intermediate Similarity	NPC190286
0.8261	Intermediate Similarity	NPC259306
0.8261	Intermediate Similarity	NPC470628
0.8261	Intermediate Similarity	NPC270478
0.8261	Intermediate Similarity	NPC251236
0.8261	Intermediate Similarity	NPC148458
0.8261	Intermediate Similarity	NPC40632
0.8261	Intermediate Similarity	NPC477509
0.8257	Intermediate Similarity	NPC99266
0.8257	Intermediate Similarity	NPC159533
0.8257	Intermediate Similarity	NPC475871
0.8257	Intermediate Similarity	NPC23584
0.8257	Intermediate Similarity	NPC472755
0.8257	Intermediate Similarity	NPC474775
0.8257	Intermediate Similarity	NPC472747
0.8257	Intermediate Similarity	NPC475945
0.8257	Intermediate Similarity	NPC4620
0.8257	Intermediate Similarity	NPC472750
0.825	Intermediate Similarity	NPC181999
0.825	Intermediate Similarity	NPC293112
0.8246	Intermediate Similarity	NPC51978
0.8246	Intermediate Similarity	NPC101965
0.8246	Intermediate Similarity	NPC477126
0.8246	Intermediate Similarity	NPC475966
0.8246	Intermediate Similarity	NPC101400
0.8246	Intermediate Similarity	NPC49451
0.8241	Intermediate Similarity	NPC471412
0.8241	Intermediate Similarity	NPC472753
0.8235	Intermediate Similarity	NPC105926
0.8235	Intermediate Similarity	NPC265557
0.8235	Intermediate Similarity	NPC91693
0.8235	Intermediate Similarity	NPC18945
0.823	Intermediate Similarity	NPC469655
0.823	Intermediate Similarity	NPC469656
0.823	Intermediate Similarity	NPC475480
0.823	Intermediate Similarity	NPC474846
0.823	Intermediate Similarity	NPC475668
0.823	Intermediate Similarity	NPC473921
0.8224	Intermediate Similarity	NPC216478
0.8224	Intermediate Similarity	NPC222303
0.822	Intermediate Similarity	NPC67569
0.8214	Intermediate Similarity	NPC137911
0.8214	Intermediate Similarity	NPC42662
0.8214	Intermediate Similarity	NPC228477
0.8214	Intermediate Similarity	NPC478210
0.8214	Intermediate Similarity	NPC469370
0.8205	Intermediate Similarity	NPC475041
0.8205	Intermediate Similarity	NPC5292
0.8205	Intermediate Similarity	NPC268958
0.8205	Intermediate Similarity	NPC180640
0.8205	Intermediate Similarity	NPC473636
0.8205	Intermediate Similarity	NPC77689
0.8198	Intermediate Similarity	NPC112780
0.8198	Intermediate Similarity	NPC143609
0.8198	Intermediate Similarity	NPC230541
0.819	Intermediate Similarity	NPC284068
0.819	Intermediate Similarity	NPC470775
0.819	Intermediate Similarity	NPC477129
0.819	Intermediate Similarity	NPC134430
0.819	Intermediate Similarity	NPC477130
0.819	Intermediate Similarity	NPC176513
0.8182	Intermediate Similarity	NPC118911
0.8182	Intermediate Similarity	NPC471940
0.8182	Intermediate Similarity	NPC476008
0.8182	Intermediate Similarity	NPC472748
0.8174	Intermediate Similarity	NPC469877
0.8174	Intermediate Similarity	NPC470919
0.8174	Intermediate Similarity	NPC473798
0.8173	Intermediate Similarity	NPC184463
0.8173	Intermediate Similarity	NPC30515
0.8167	Intermediate Similarity	NPC172154
0.8167	Intermediate Similarity	NPC81736
0.8165	Intermediate Similarity	NPC137430
0.8165	Intermediate Similarity	NPC472754
0.8165	Intermediate Similarity	NPC474747
0.8165	Intermediate Similarity	NPC476081
0.8165	Intermediate Similarity	NPC11956
0.8165	Intermediate Similarity	NPC162973
0.8158	Intermediate Similarity	NPC98038
0.8158	Intermediate Similarity	NPC470025
0.8158	Intermediate Similarity	NPC302146
0.8158	Intermediate Similarity	NPC194951
0.8158	Intermediate Similarity	NPC321272
0.8158	Intermediate Similarity	NPC474516
0.8158	Intermediate Similarity	NPC90952
0.8158	Intermediate Similarity	NPC328074
0.8158	Intermediate Similarity	NPC12046
0.8158	Intermediate Similarity	NPC313921
0.8158	Intermediate Similarity	NPC277769
0.8158	Intermediate Similarity	NPC317460
0.8151	Intermediate Similarity	NPC162009
0.8151	Intermediate Similarity	NPC470265
0.8151	Intermediate Similarity	NPC257017
0.8151	Intermediate Similarity	NPC222688

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 NPC469463 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	170
0.1-0.2	1176
0.2-0.3	3311
0.3-0.4	2736
0.4-0.5	1076
0.5-0.6	381
0.6-0.7	213
0.7-0.8	87
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
0.789	Intermediate Similarity	NPD4225	Approved
0.7881	Intermediate Similarity	NPD7115	Discovery
0.7807	Intermediate Similarity	NPD6686	Approved
0.7778	Intermediate Similarity	NPD4632	Approved
0.7692	Intermediate Similarity	NPD8297	Approved
0.7686	Intermediate Similarity	NPD6319	Approved
0.7652	Intermediate Similarity	NPD6881	Approved
0.7652	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7652	Intermediate Similarity	NPD6899	Approved
0.7638	Intermediate Similarity	NPD7260	Phase 2
0.7623	Intermediate Similarity	NPD8513	Phase 3
0.7623	Intermediate Similarity	NPD8517	Approved
0.7623	Intermediate Similarity	NPD8516	Approved
0.7623	Intermediate Similarity	NPD8515	Approved
0.7607	Intermediate Similarity	NPD6650	Approved
0.7607	Intermediate Similarity	NPD6649	Approved
0.7593	Intermediate Similarity	NPD5779	Approved
0.7593	Intermediate Similarity	NPD5778	Approved
0.7586	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7581	Intermediate Similarity	NPD7492	Approved
0.7565	Intermediate Similarity	NPD5697	Approved
0.7565	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.7541	Intermediate Similarity	NPD6054	Approved
0.7521	Intermediate Similarity	NPD7102	Approved
0.7521	Intermediate Similarity	NPD6371	Approved
0.7521	Intermediate Similarity	NPD7290	Approved
0.7521	Intermediate Similarity	NPD6883	Approved
0.752	Intermediate Similarity	NPD6616	Approved
0.75	Intermediate Similarity	NPD7983	Approved
0.75	Intermediate Similarity	NPD7640	Approved
0.75	Intermediate Similarity	NPD7639	Approved
0.7478	Intermediate Similarity	NPD5739	Approved
0.7478	Intermediate Similarity	NPD6675	Approved
0.7478	Intermediate Similarity	NPD7128	Approved
0.7478	Intermediate Similarity	NPD6402	Approved
0.746	Intermediate Similarity	NPD7078	Approved
0.7458	Intermediate Similarity	NPD8130	Phase 1
0.7458	Intermediate Similarity	NPD6617	Approved
0.7458	Intermediate Similarity	NPD6869	Approved
0.7458	Intermediate Similarity	NPD6847	Approved
0.7458	Intermediate Similarity	NPD8413	Clinical (unspecified phase)
0.7438	Intermediate Similarity	NPD6009	Approved
0.7436	Intermediate Similarity	NPD6012	Approved
0.7436	Intermediate Similarity	NPD6013	Approved
0.7436	Intermediate Similarity	NPD6014	Approved
0.7436	Intermediate Similarity	NPD6373	Approved
0.7436	Intermediate Similarity	NPD6372	Approved
0.7434	Intermediate Similarity	NPD5344	Discontinued
0.7419	Intermediate Similarity	NPD6370	Approved
0.7411	Intermediate Similarity	NPD7638	Approved
0.7411	Intermediate Similarity	NPD8029	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD7838	Discovery
0.7407	Intermediate Similarity	NPD46	Approved
0.7407	Intermediate Similarity	NPD6698	Approved
0.7402	Intermediate Similarity	NPD7736	Approved
0.7395	Intermediate Similarity	NPD6882	Approved
0.7395	Intermediate Similarity	NPD6053	Discontinued
0.7381	Intermediate Similarity	NPD7507	Approved
0.7373	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7368	Intermediate Similarity	NPD5211	Phase 2
0.736	Intermediate Similarity	NPD7604	Phase 2
0.735	Intermediate Similarity	NPD6011	Approved
0.735	Intermediate Similarity	NPD7320	Approved
0.7345	Intermediate Similarity	NPD6648	Approved
0.7339	Intermediate Similarity	NPD5983	Phase 2
0.7339	Intermediate Similarity	NPD6015	Approved
0.7339	Intermediate Similarity	NPD7503	Approved
0.7339	Intermediate Similarity	NPD6016	Approved
0.7323	Intermediate Similarity	NPD8074	Phase 3
0.7308	Intermediate Similarity	NPD6845	Suspended
0.7297	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.728	Intermediate Similarity	NPD5988	Approved
0.7265	Intermediate Similarity	NPD5701	Approved
0.7264	Intermediate Similarity	NPD1694	Approved
0.7258	Intermediate Similarity	NPD6059	Approved
0.7244	Intermediate Similarity	NPD6336	Discontinued
0.7241	Intermediate Similarity	NPD5141	Approved
0.7227	Intermediate Similarity	NPD4634	Approved
0.7222	Intermediate Similarity	NPD8328	Phase 3
0.7209	Intermediate Similarity	NPD7319	Approved
0.7193	Intermediate Similarity	NPD5285	Approved
0.7193	Intermediate Similarity	NPD4696	Approved
0.7193	Intermediate Similarity	NPD5286	Approved
0.7188	Intermediate Similarity	NPD8293	Discontinued
0.7182	Intermediate Similarity	NPD6411	Approved
0.7179	Intermediate Similarity	NPD6008	Approved
0.7168	Intermediate Similarity	NPD6083	Phase 2
0.7168	Intermediate Similarity	NPD6084	Phase 2
0.7119	Intermediate Similarity	NPD6412	Phase 2
0.7119	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.709	Intermediate Similarity	NPD7966	Clinical (unspecified phase)
0.7069	Intermediate Similarity	NPD5226	Approved
0.7069	Intermediate Similarity	NPD5224	Approved
0.7069	Intermediate Similarity	NPD5225	Approved
0.7069	Intermediate Similarity	NPD4633	Approved
0.7054	Intermediate Similarity	NPD5282	Discontinued
0.704	Intermediate Similarity	NPD7101	Approved
0.704	Intermediate Similarity	NPD7100	Approved
0.7027	Intermediate Similarity	NPD7637	Suspended
0.7025	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.7018	Intermediate Similarity	NPD4755	Approved
0.7016	Intermediate Similarity	NPD8295	Clinical (unspecified phase)
0.7009	Intermediate Similarity	NPD5174	Approved
0.7009	Intermediate Similarity	NPD5175	Approved
0.7	Intermediate Similarity	NPD5764	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD6101	Approved
0.6991	Remote Similarity	NPD5695	Phase 3
0.6983	Remote Similarity	NPD5223	Approved
0.6981	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6964	Remote Similarity	NPD6399	Phase 3
0.696	Remote Similarity	NPD6335	Approved
0.6957	Remote Similarity	NPD5696	Approved
0.6944	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6937	Remote Similarity	NPD5785	Approved
0.6935	Remote Similarity	NPD6274	Approved
0.693	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.693	Remote Similarity	NPD5221	Approved
0.693	Remote Similarity	NPD5222	Approved
0.6929	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD6921	Approved
0.6923	Remote Similarity	NPD7632	Discontinued
0.6897	Remote Similarity	NPD4700	Approved
0.688	Remote Similarity	NPD6317	Approved
0.6875	Remote Similarity	NPD5284	Approved
0.6875	Remote Similarity	NPD5281	Approved
0.6875	Remote Similarity	NPD6079	Approved
0.687	Remote Similarity	NPD7902	Approved
0.687	Remote Similarity	NPD5173	Approved
0.6842	Remote Similarity	NPD4629	Approved
0.6842	Remote Similarity	NPD5210	Approved
0.6825	Remote Similarity	NPD7328	Approved
0.6825	Remote Similarity	NPD7327	Approved
0.6825	Remote Similarity	NPD6314	Approved
0.6825	Remote Similarity	NPD6313	Approved
0.6818	Remote Similarity	NPD7524	Approved
0.68	Remote Similarity	NPD6868	Approved
0.6797	Remote Similarity	NPD8033	Approved
0.6783	Remote Similarity	NPD4697	Phase 3
0.6777	Remote Similarity	NPD4730	Approved
0.6777	Remote Similarity	NPD4729	Approved
0.6772	Remote Similarity	NPD7516	Approved
0.6757	Remote Similarity	NPD6672	Approved
0.6757	Remote Similarity	NPD5737	Approved
0.6754	Remote Similarity	NPD7748	Approved
0.6742	Remote Similarity	NPD6033	Approved
0.6727	Remote Similarity	NPD5279	Phase 3
0.6726	Remote Similarity	NPD6050	Approved
0.6726	Remote Similarity	NPD7515	Phase 2
0.6726	Remote Similarity	NPD5693	Phase 1
0.6726	Remote Similarity	NPD5694	Approved
0.6721	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6719	Remote Similarity	NPD8377	Approved
0.6719	Remote Similarity	NPD8294	Approved
0.6697	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6696	Remote Similarity	NPD5328	Approved
0.6696	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.6696	Remote Similarity	NPD4753	Phase 2
0.6667	Remote Similarity	NPD8380	Approved
0.6667	Remote Similarity	NPD8335	Approved
0.6667	Remote Similarity	NPD5248	Approved
0.6667	Remote Similarity	NPD5247	Approved
0.6667	Remote Similarity	NPD8379	Approved
0.6667	Remote Similarity	NPD8296	Approved
0.6667	Remote Similarity	NPD5251	Approved
0.6667	Remote Similarity	NPD6908	Approved
0.6667	Remote Similarity	NPD5250	Approved
0.6667	Remote Similarity	NPD5249	Phase 3
0.6667	Remote Similarity	NPD6909	Approved
0.6667	Remote Similarity	NPD3573	Approved
0.6667	Remote Similarity	NPD8378	Approved
0.664	Remote Similarity	NPD8133	Approved
0.6639	Remote Similarity	NPD5128	Approved
0.6638	Remote Similarity	NPD7839	Suspended
0.6637	Remote Similarity	NPD5207	Approved
0.6637	Remote Similarity	NPD5692	Phase 3
0.6636	Remote Similarity	NPD1696	Phase 3
0.6613	Remote Similarity	NPD5216	Approved
0.6613	Remote Similarity	NPD5215	Approved
0.6613	Remote Similarity	NPD5217	Approved
0.6612	Remote Similarity	NPD4767	Approved
0.6612	Remote Similarity	NPD4768	Approved
0.6609	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6609	Remote Similarity	NPD7900	Approved
0.6606	Remote Similarity	NPD6110	Phase 1
0.6606	Remote Similarity	NPD6695	Phase 3
0.6583	Remote Similarity	NPD4754	Approved
0.6577	Remote Similarity	NPD6684	Approved
0.6577	Remote Similarity	NPD7334	Approved
0.6577	Remote Similarity	NPD6409	Approved
0.6577	Remote Similarity	NPD7146	Approved
0.6577	Remote Similarity	NPD3618	Phase 1
0.6577	Remote Similarity	NPD5330	Approved
0.6577	Remote Similarity	NPD7521	Approved
0.6565	Remote Similarity	NPD7829	Approved
0.6565	Remote Similarity	NPD7830	Approved
0.6552	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD7236	Approved
0.6549	Remote Similarity	NPD1695	Approved
0.6549	Remote Similarity	NPD6673	Approved
0.6549	Remote Similarity	NPD6080	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