NPASS Compound

Structure

NPC475900 OpenBabel07101719252D 28 29 0 0 1 0 0 0 0 0999 V2000 -1.4070 3.6599 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5706 3.3619 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2160 -0.1827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3959 0.4945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0773 -2.5865 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2619 2.9945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0417 2.7291 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9324 -1.2873 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0016 -1.6526 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5299 1.9945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0528 2.5800 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 3.2272 -0.3317 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3959 1.4945 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 0.2412 -1.6000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1355 -1.1526 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6639 1.4945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9865 -0.1638 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6667 0.5692 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3125 1.6491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4606 -0.8876 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6639 0.4945 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7978 1.9945 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3110 0.8673 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4495 -1.0366 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5299 0.9945 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2619 1.9945 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 1.3013 1.5001 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 7 1 0 0 0 0 2 11 1 0 0 0 0 3 12 1 0 0 0 0 4 13 1 0 0 0 0 5 14 2 0 0 0 0 6 26 1 0 0 0 0 7 11 1 0 0 0 0 8 9 1 0 0 0 0 8 12 1 0 0 0 0 10 13 1 0 0 0 0 10 16 1 0 0 0 0 11 19 1 0 0 0 0 12 21 1 1 0 0 0 13 26 1 0 0 0 0 14 15 1 0 0 0 0 14 20 1 0 0 0 0 15 9 1 6 0 0 0 15 17 1 0 0 0 0 16 21 1 0 0 0 0 16 22 2 0 0 0 0 17 18 1 0 0 0 0 17 27 1 1 0 0 0 18 21 1 6 0 0 0 18 28 1 0 0 0 0 19 23 2 0 0 0 0 19 28 1 0 0 0 0 20 24 2 0 0 0 0 20 27 1 0 0 0 0 21 25 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	396.21
Volume:	405.645
LogP:	2.545
LogD:	2.001
LogS:	-3.571
# Rotatable Bonds:	8
TPSA:	99.13
# H-Bond Aceptor:	7
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.52
Synthetic Accessibility Score:	4.791
Fsp3:	0.762
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.686
MDCK Permeability:	4.3674772314261645e-05
Pgp-inhibitor:	0.953
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.018
20% Bioavailability (F20%):	0.074
30% Bioavailability (F30%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.851
Plasma Protein Binding (PPB):	67.6453628540039%
Volume Distribution (VD):	0.907
Pgp-substrate:	46.00511932373047%

ADMET: Metabolism

CYP1A2-inhibitor:	0.07
CYP1A2-substrate:	0.121
CYP2C19-inhibitor:	0.026
CYP2C19-substrate:	0.779
CYP2C9-inhibitor:	0.031
CYP2C9-substrate:	0.037
CYP2D6-inhibitor:	0.01
CYP2D6-substrate:	0.125
CYP3A4-inhibitor:	0.446
CYP3A4-substrate:	0.381

ADMET: Excretion

Clearance (CL):	8.909
Half-life (T1/2):	0.15

ADMET: Toxicity

hERG Blockers:	0.021
Human Hepatotoxicity (H-HT):	0.823
Drug-inuced Liver Injury (DILI):	0.791
AMES Toxicity:	0.039
Rat Oral Acute Toxicity:	0.372
Maximum Recommended Daily Dose:	0.045
Skin Sensitization:	0.472
Carcinogencity:	0.422
Eye Corrosion:	0.055
Eye Irritation:	0.048
Respiratory Toxicity:	0.968

Download Data

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

Natural Product: NPC475900

Natural Product ID:	NPC475900
*Common Name:**	(1S,5S,6R,7S,9R,10R)-1-Hydroxy-4-Methoxy-5-Methylbutanoyloxy-2,9-Dioxaxanth-11-En-6,12-Olide
IUPAC Name:	[(3aR,6S,7S,8S,8aR)-7-hydroxy-7-(3-methoxybutanoyl)-6-methyl-3-methylidene-2-oxo-3a,4,5,6,8,8a-hexahydrocyclohepta[b]furan-8-yl] 2-methylbutanoate
Synonyms:
Standard InCHIKey:	JAAHNMMVUXTONO-JGOFBEHASA-N
Standard InCHI:	InChI=1S/C21H32O7/c1-7-11(2)19(23)28-18-17-15(14(5)20(24)27-17)9-8-12(3)21(18,25)16(22)10-13(4)26-6/h11-13,15,17-18,25H,5,7-10H2,1-4,6H3/t11?,12-,13?,15+,17+,18-,21+/m0/s1
SMILES:	COC(CC(=O)[C@]1(O)[C@@H](C)CC[C@H]2[C@H]([C@@H]1OC(=O)C(CC)C)OC(=O)C2=C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL518145
PubChem CID:	44575376
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene 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
NPO21597	Ratibida columnifera	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10579870]
NPO21597	Ratibida columnifera	Species	Asteraceae	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	7

Activity Type	# Activity
Cell Line	4
NON-MOLECULAR	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1034	Cell Line	Lu1	Homo sapiens	ED50	=	4.4	ug ml-1	PMID[536595]
NPT1851	Cell Line	Col2	Homo sapiens	ED50	=	3.1	ug ml-1	PMID[536595]
NPT91	Cell Line	KB	Homo sapiens	ED50	=	6.6	ug ml-1	PMID[536595]
NPT858	Cell Line	LNCaP	Homo sapiens	ED50	=	0.5	ug ml-1	PMID[536595]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	1.2	ug ml-1	PMID[536595]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	5.0	ug ml-1	PMID[536595]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	4.0	ug ml-1	PMID[536595]

☑ 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 NPC475900 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	252
0.1-0.2	1778
0.2-0.3	5968
0.3-0.4	10115
0.4-0.5	13448
0.5-0.6	7028
0.6-0.7	3184
0.7-0.8	773
0.8-0.85	122
0.85-0.9	21
0.9-0.95	6
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9667	High Similarity	NPC476009
0.9239	High Similarity	NPC470883
0.9239	High Similarity	NPC158416
0.9239	High Similarity	NPC39859
0.9239	High Similarity	NPC76862
0.9158	High Similarity	NPC474747
0.9062	High Similarity	NPC475945
0.9062	High Similarity	NPC475871
0.9053	High Similarity	NPC474742
0.9	High Similarity	NPC474951
0.8969	High Similarity	NPC474741
0.8936	High Similarity	NPC474313
0.8866	High Similarity	NPC475873
0.883	High Similarity	NPC31645
0.8817	High Similarity	NPC190294
0.8791	High Similarity	NPC173926
0.8778	High Similarity	NPC190753
0.8737	High Similarity	NPC328562
0.8737	High Similarity	NPC323421
0.8723	High Similarity	NPC163228
0.8681	High Similarity	NPC58219
0.8681	High Similarity	NPC177629
0.8667	High Similarity	NPC475019
0.8667	High Similarity	NPC476015
0.8667	High Similarity	NPC474949
0.8667	High Similarity	NPC474762
0.866	High Similarity	NPC47880
0.8602	High Similarity	NPC184463
0.8602	High Similarity	NPC329952
0.8587	High Similarity	NPC307411
0.8587	High Similarity	NPC92974
0.8571	High Similarity	NPC149371
0.8571	High Similarity	NPC186148
0.8571	High Similarity	NPC118601
0.8556	High Similarity	NPC149725
0.8556	High Similarity	NPC329749
0.8556	High Similarity	NPC47958
0.8556	High Similarity	NPC304509
0.8542	High Similarity	NPC471150
0.8511	High Similarity	NPC473263
0.8511	High Similarity	NPC475788
0.8511	High Similarity	NPC473234
0.8511	High Similarity	NPC308656
0.8511	High Similarity	NPC60386
0.8511	High Similarity	NPC153590
0.8511	High Similarity	NPC473273
0.8511	High Similarity	NPC476300
0.8495	Intermediate Similarity	NPC51004
0.8478	Intermediate Similarity	NPC178875
0.8478	Intermediate Similarity	NPC53158
0.8469	Intermediate Similarity	NPC15993
0.8469	Intermediate Similarity	NPC201718
0.8462	Intermediate Similarity	NPC470242
0.8444	Intermediate Similarity	NPC474780
0.8438	Intermediate Similarity	NPC142529
0.8438	Intermediate Similarity	NPC91771
0.8421	Intermediate Similarity	NPC473331
0.8416	Intermediate Similarity	NPC26617
0.8404	Intermediate Similarity	NPC30515
0.8404	Intermediate Similarity	NPC184063
0.84	Intermediate Similarity	NPC203659
0.8384	Intermediate Similarity	NPC225353
0.8384	Intermediate Similarity	NPC320019
0.8384	Intermediate Similarity	NPC324017
0.8367	Intermediate Similarity	NPC186861
0.8351	Intermediate Similarity	NPC311904
0.8333	Intermediate Similarity	NPC36954
0.8317	Intermediate Similarity	NPC44004
0.8316	Intermediate Similarity	NPC212486
0.8316	Intermediate Similarity	NPC475912
0.83	Intermediate Similarity	NPC472755
0.83	Intermediate Similarity	NPC110989
0.8298	Intermediate Similarity	NPC65359
0.8298	Intermediate Similarity	NPC19087
0.8283	Intermediate Similarity	NPC164598
0.8283	Intermediate Similarity	NPC472753
0.8283	Intermediate Similarity	NPC474339
0.8283	Intermediate Similarity	NPC476270
0.828	Intermediate Similarity	NPC202672
0.8265	Intermediate Similarity	NPC471144
0.8242	Intermediate Similarity	NPC151176
0.8242	Intermediate Similarity	NPC3464
0.8242	Intermediate Similarity	NPC475963
0.8224	Intermediate Similarity	NPC471146
0.8224	Intermediate Similarity	NPC471145
0.8218	Intermediate Similarity	NPC100487
0.8211	Intermediate Similarity	NPC12172
0.8211	Intermediate Similarity	NPC208886
0.8211	Intermediate Similarity	NPC475881
0.8211	Intermediate Similarity	NPC70251
0.8211	Intermediate Similarity	NPC469627
0.8211	Intermediate Similarity	NPC286341
0.8211	Intermediate Similarity	NPC191339
0.8202	Intermediate Similarity	NPC474981
0.82	Intermediate Similarity	NPC472754
0.8191	Intermediate Similarity	NPC168679
0.8191	Intermediate Similarity	NPC38392
0.8191	Intermediate Similarity	NPC12872
0.8182	Intermediate Similarity	NPC471381
0.8172	Intermediate Similarity	NPC5130
0.8163	Intermediate Similarity	NPC108475
0.8163	Intermediate Similarity	NPC170143
0.8163	Intermediate Similarity	NPC213947
0.8144	Intermediate Similarity	NPC475659
0.8144	Intermediate Similarity	NPC270013
0.8144	Intermediate Similarity	NPC14961
0.8144	Intermediate Similarity	NPC476053
0.8144	Intermediate Similarity	NPC472873
0.8132	Intermediate Similarity	NPC257358
0.8132	Intermediate Similarity	NPC474472
0.8132	Intermediate Similarity	NPC128429
0.8125	Intermediate Similarity	NPC200237
0.8125	Intermediate Similarity	NPC135776
0.8125	Intermediate Similarity	NPC179746
0.8125	Intermediate Similarity	NPC81419
0.8119	Intermediate Similarity	NPC473148
0.8105	Intermediate Similarity	NPC476004
0.8105	Intermediate Similarity	NPC474323
0.8105	Intermediate Similarity	NPC474761
0.8105	Intermediate Similarity	NPC206614
0.81	Intermediate Similarity	NPC110443
0.81	Intermediate Similarity	NPC133907
0.81	Intermediate Similarity	NPC46998
0.81	Intermediate Similarity	NPC171759
0.81	Intermediate Similarity	NPC128733
0.81	Intermediate Similarity	NPC185141
0.809	Intermediate Similarity	NPC19841
0.8085	Intermediate Similarity	NPC207114
0.8085	Intermediate Similarity	NPC217983
0.8085	Intermediate Similarity	NPC79549
0.8077	Intermediate Similarity	NPC38154
0.8065	Intermediate Similarity	NPC304558
0.8065	Intermediate Similarity	NPC309757
0.8065	Intermediate Similarity	NPC236692
0.8065	Intermediate Similarity	NPC238593
0.8061	Intermediate Similarity	NPC476315
0.8061	Intermediate Similarity	NPC473859
0.8058	Intermediate Similarity	NPC477513
0.8041	Intermediate Similarity	NPC81386
0.8041	Intermediate Similarity	NPC474035
0.8039	Intermediate Similarity	NPC472756
0.8021	Intermediate Similarity	NPC20713
0.8021	Intermediate Similarity	NPC133698
0.802	Intermediate Similarity	NPC471148
0.8	Intermediate Similarity	NPC475949
0.8	Intermediate Similarity	NPC215556
0.8	Intermediate Similarity	NPC477103
0.8	Intermediate Similarity	NPC288876
0.7981	Intermediate Similarity	NPC255082
0.798	Intermediate Similarity	NPC181151
0.7979	Intermediate Similarity	NPC248602
0.7979	Intermediate Similarity	NPC201658
0.7961	Intermediate Similarity	NPC54737
0.7961	Intermediate Similarity	NPC223450
0.7961	Intermediate Similarity	NPC243998
0.7941	Intermediate Similarity	NPC4620
0.7938	Intermediate Similarity	NPC469645
0.7938	Intermediate Similarity	NPC469692
0.7917	Intermediate Similarity	NPC54065
0.7917	Intermediate Similarity	NPC297474
0.7917	Intermediate Similarity	NPC216284
0.7917	Intermediate Similarity	NPC475748
0.7905	Intermediate Similarity	NPC477102
0.79	Intermediate Similarity	NPC474213
0.79	Intermediate Similarity	NPC45125
0.7872	Intermediate Similarity	NPC475491
0.7872	Intermediate Similarity	NPC469626
0.7872	Intermediate Similarity	NPC162071
0.7872	Intermediate Similarity	NPC187661
0.7864	Intermediate Similarity	NPC220964
0.7864	Intermediate Similarity	NPC475676
0.7857	Intermediate Similarity	NPC477131
0.7857	Intermediate Similarity	NPC121825
0.7857	Intermediate Similarity	NPC198853
0.7843	Intermediate Similarity	NPC86077
0.7843	Intermediate Similarity	NPC80144
0.7835	Intermediate Similarity	NPC155215
0.7835	Intermediate Similarity	NPC171360
0.7835	Intermediate Similarity	NPC293001
0.7835	Intermediate Similarity	NPC63193
0.7835	Intermediate Similarity	NPC133888
0.7835	Intermediate Similarity	NPC131209
0.7835	Intermediate Similarity	NPC35959
0.7835	Intermediate Similarity	NPC29821
0.7835	Intermediate Similarity	NPC57304
0.783	Intermediate Similarity	NPC257240
0.7826	Intermediate Similarity	NPC246076
0.7812	Intermediate Similarity	NPC155935
0.7812	Intermediate Similarity	NPC32922
0.7812	Intermediate Similarity	NPC151770
0.781	Intermediate Similarity	NPC68248
0.78	Intermediate Similarity	NPC111348
0.78	Intermediate Similarity	NPC169205
0.78	Intermediate Similarity	NPC40812
0.7789	Intermediate Similarity	NPC231889
0.7789	Intermediate Similarity	NPC179659
0.7788	Intermediate Similarity	NPC474101
0.7788	Intermediate Similarity	NPC9303
0.7788	Intermediate Similarity	NPC16313
0.7778	Intermediate Similarity	NPC471142

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 NPC475900 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	312
0.1-0.2	2552
0.2-0.3	3666
0.3-0.4	1692
0.4-0.5	600
0.5-0.6	278
0.6-0.7	45
0.7-0.8	4
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8416	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.783	Intermediate Similarity	NPD6371	Approved
0.7778	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7396	Intermediate Similarity	NPD1733	Clinical (unspecified phase)
0.7315	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.73	Intermediate Similarity	NPD7983	Approved
0.7273	Intermediate Similarity	NPD1695	Approved
0.72	Intermediate Similarity	NPD46	Approved
0.72	Intermediate Similarity	NPD6698	Approved
0.7157	Intermediate Similarity	NPD5282	Discontinued
0.6964	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6863	Remote Similarity	NPD7838	Discovery
0.6731	Remote Similarity	NPD5778	Approved
0.6731	Remote Similarity	NPD5779	Approved
0.6729	Remote Similarity	NPD4225	Approved
0.6723	Remote Similarity	NPD8516	Approved
0.6723	Remote Similarity	NPD8517	Approved
0.6723	Remote Similarity	NPD8515	Approved
0.6723	Remote Similarity	NPD8513	Phase 3
0.6699	Remote Similarity	NPD5785	Approved
0.6696	Remote Similarity	NPD6686	Approved
0.6639	Remote Similarity	NPD6319	Approved
0.6634	Remote Similarity	NPD5786	Approved
0.6633	Remote Similarity	NPD5369	Approved
0.6609	Remote Similarity	NPD6053	Discontinued
0.6583	Remote Similarity	NPD6921	Approved
0.6566	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6566	Remote Similarity	NPD6435	Approved
0.6557	Remote Similarity	NPD7492	Approved
0.6535	Remote Similarity	NPD5363	Approved
0.6525	Remote Similarity	NPD7115	Discovery
0.6512	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6504	Remote Similarity	NPD6616	Approved
0.65	Remote Similarity	NPD6054	Approved
0.6455	Remote Similarity	NPD5344	Discontinued
0.6452	Remote Similarity	NPD8074	Phase 3
0.6452	Remote Similarity	NPD7078	Approved
0.6446	Remote Similarity	NPD8269	Approved
0.6446	Remote Similarity	NPD8267	Approved
0.6446	Remote Similarity	NPD8268	Approved
0.6446	Remote Similarity	NPD8266	Approved
0.6442	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6442	Remote Similarity	NPD6101	Approved
0.6422	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.641	Remote Similarity	NPD4632	Approved
0.64	Remote Similarity	NPD4269	Approved
0.64	Remote Similarity	NPD7736	Approved
0.64	Remote Similarity	NPD4270	Approved
0.6393	Remote Similarity	NPD6370	Approved
0.6364	Remote Similarity	NPD5368	Approved
0.6364	Remote Similarity	NPD6059	Approved
0.6341	Remote Similarity	NPD8328	Phase 3
0.6341	Remote Similarity	NPD7642	Approved
0.6325	Remote Similarity	NPD8297	Approved
0.6321	Remote Similarity	NPD6411	Approved
0.632	Remote Similarity	NPD8293	Discontinued
0.6311	Remote Similarity	NPD6016	Approved
0.6311	Remote Similarity	NPD6015	Approved
0.6271	Remote Similarity	NPD8133	Approved
0.6261	Remote Similarity	NPD6899	Approved
0.6261	Remote Similarity	NPD6881	Approved
0.626	Remote Similarity	NPD5988	Approved
0.626	Remote Similarity	NPD8080	Discontinued
0.625	Remote Similarity	NPD4250	Approved
0.625	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.625	Remote Similarity	NPD4251	Approved
0.625	Remote Similarity	NPD7260	Phase 2
0.6239	Remote Similarity	NPD2204	Approved
0.6239	Remote Similarity	NPD7839	Suspended
0.6239	Remote Similarity	NPD6650	Approved
0.6239	Remote Similarity	NPD6649	Approved
0.6228	Remote Similarity	NPD6675	Approved
0.6228	Remote Similarity	NPD5739	Approved
0.6228	Remote Similarity	NPD6402	Approved
0.6228	Remote Similarity	NPD7128	Approved
0.622	Remote Similarity	NPD7319	Approved
0.6216	Remote Similarity	NPD6648	Approved
0.6207	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6207	Remote Similarity	NPD6373	Approved
0.6207	Remote Similarity	NPD6372	Approved
0.6202	Remote Similarity	NPD6845	Suspended
0.62	Remote Similarity	NPD4252	Approved
0.6179	Remote Similarity	NPD8274	Clinical (unspecified phase)
0.6176	Remote Similarity	NPD6110	Phase 1
0.6176	Remote Similarity	NPD7154	Phase 3
0.6174	Remote Similarity	NPD5697	Approved
0.6154	Remote Similarity	NPD7102	Approved
0.6154	Remote Similarity	NPD6883	Approved
0.6154	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6154	Remote Similarity	NPD7290	Approved
0.6154	Remote Similarity	NPD4634	Approved
0.6154	Remote Similarity	NPD4249	Approved
0.614	Remote Similarity	NPD4057	Clinical (unspecified phase)
0.614	Remote Similarity	NPD4056	Clinical (unspecified phase)
0.6121	Remote Similarity	NPD7320	Approved
0.6116	Remote Similarity	NPD6009	Approved
0.6111	Remote Similarity	NPD8451	Approved
0.6111	Remote Similarity	NPD7507	Approved
0.6111	Remote Similarity	NPD8273	Phase 1
0.6111	Remote Similarity	NPD6399	Phase 3
0.6102	Remote Similarity	NPD8130	Phase 1
0.6102	Remote Similarity	NPD6617	Approved
0.6102	Remote Similarity	NPD6869	Approved
0.6102	Remote Similarity	NPD6847	Approved
0.6087	Remote Similarity	NPD6008	Approved
0.608	Remote Similarity	NPD7830	Approved
0.608	Remote Similarity	NPD7829	Approved
0.608	Remote Similarity	NPD7604	Phase 2
0.6068	Remote Similarity	NPD6013	Approved
0.6068	Remote Similarity	NPD6014	Approved
0.6068	Remote Similarity	NPD6012	Approved
0.6066	Remote Similarity	NPD7641	Discontinued
0.6063	Remote Similarity	NPD8448	Approved
0.6058	Remote Similarity	NPD1694	Approved
0.6058	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.605	Remote Similarity	NPD6882	Approved
0.6048	Remote Similarity	NPD8444	Approved
0.6048	Remote Similarity	NPD5983	Phase 2
0.604	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.604	Remote Similarity	NPD4822	Approved
0.604	Remote Similarity	NPD4821	Approved
0.604	Remote Similarity	NPD4819	Approved
0.604	Remote Similarity	NPD4820	Approved
0.6036	Remote Similarity	NPD6084	Phase 2
0.6036	Remote Similarity	NPD6083	Phase 2
0.6034	Remote Similarity	NPD6412	Phase 2
0.6034	Remote Similarity	NPD5701	Approved
0.6019	Remote Similarity	NPD5362	Discontinued
0.6018	Remote Similarity	NPD1700	Approved
0.6	Remote Similarity	NPD4802	Phase 2
0.6	Remote Similarity	NPD5695	Phase 3
0.6	Remote Similarity	NPD4238	Approved
0.5984	Remote Similarity	NPD6336	Discontinued
0.5984	Remote Similarity	NPD8137	Clinical (unspecified phase)
0.5983	Remote Similarity	NPD6011	Approved
0.5982	Remote Similarity	NPD5696	Approved
0.5982	Remote Similarity	NPD7638	Approved
0.5929	Remote Similarity	NPD7640	Approved
0.5929	Remote Similarity	NPD7639	Approved
0.5923	Remote Similarity	NPD8391	Approved
0.5923	Remote Similarity	NPD8390	Approved
0.5923	Remote Similarity	NPD8392	Approved
0.5922	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.5922	Remote Similarity	NPD5209	Approved
0.5906	Remote Similarity	NPD8341	Approved
0.5906	Remote Similarity	NPD8342	Approved
0.5906	Remote Similarity	NPD8340	Approved
0.5906	Remote Similarity	NPD8299	Approved
0.5897	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.5891	Remote Similarity	NPD6033	Approved
0.5872	Remote Similarity	NPD8034	Phase 2
0.5872	Remote Similarity	NPD8035	Phase 2
0.5872	Remote Similarity	NPD7637	Suspended
0.5842	Remote Similarity	NPD4268	Approved
0.5842	Remote Similarity	NPD4271	Approved
0.5842	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.5833	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.5826	Remote Similarity	NPD8083	Approved
0.5826	Remote Similarity	NPD8084	Approved
0.5826	Remote Similarity	NPD8139	Approved
0.5826	Remote Similarity	NPD8138	Approved
0.5826	Remote Similarity	NPD8085	Approved
0.5826	Remote Similarity	NPD8086	Approved
0.5826	Remote Similarity	NPD5211	Phase 2
0.5826	Remote Similarity	NPD8082	Approved
0.5821	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5806	Remote Similarity	NPD7909	Approved
0.5798	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.5789	Remote Similarity	NPD5285	Approved
0.5789	Remote Similarity	NPD5286	Approved
0.5789	Remote Similarity	NPD4696	Approved
0.5776	Remote Similarity	NPD8276	Approved
0.5776	Remote Similarity	NPD8275	Approved
0.5772	Remote Similarity	NPD6274	Approved
0.576	Remote Similarity	NPD7101	Approved
0.576	Remote Similarity	NPD7100	Approved
0.5752	Remote Similarity	NPD4755	Approved
0.5752	Remote Similarity	NPD7902	Approved
0.5746	Remote Similarity	NPD8415	Approved
0.5745	Remote Similarity	NPD7341	Phase 2
0.5741	Remote Similarity	NPD6672	Approved
0.5741	Remote Similarity	NPD5737	Approved
0.5727	Remote Similarity	NPD5693	Phase 1
0.5726	Remote Similarity	NPD7500	Approved
0.5726	Remote Similarity	NPD8081	Approved
0.5726	Remote Similarity	NPD5141	Approved
0.569	Remote Similarity	NPD5225	Approved
0.569	Remote Similarity	NPD5224	Approved
0.569	Remote Similarity	NPD5226	Approved
0.569	Remote Similarity	NPD4633	Approved
0.5688	Remote Similarity	NPD5370	Suspended
0.5684	Remote Similarity	NPD7331	Phase 2
0.5682	Remote Similarity	NPD5956	Approved
0.568	Remote Similarity	NPD6335	Approved
0.5678	Remote Similarity	NPD8393	Approved
0.5669	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.5652	Remote Similarity	NPD4700	Approved
0.5648	Remote Similarity	NPD7524	Approved
0.5641	Remote Similarity	NPD5175	Approved
0.5641	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