NPASS Compound

Structure

NPC476081 OpenBabel07101718202D 31 33 0 0 1 0 0 0 0 0999 V2000 5.0433 0.9706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9452 -2.1000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5217 0.4853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9706 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0070 -2.2964 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8406 1.4559 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8839 -0.4853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2028 -0.4853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7244 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3622 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6811 0.9706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 0.9706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6158 -1.6524 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6811 -1.9412 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0433 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6664 -1.4506 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8406 -1.4559 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.5650 -0.4853 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.5217 -0.4853 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 9.1011 -0.8118 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8406 -0.4853 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9706 -1.6811 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6811 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5217 -1.4559 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -1.9412 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 10.0664 -0.7104 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9412 -1.6811 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4853 -2.5217 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4923 -1.4559 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4517 -0.0905 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 15 1 0 0 0 0 2 16 1 0 0 0 0 6 11 1 0 0 0 0 6 12 1 0 0 0 0 7 9 1 0 0 0 0 7 15 2 0 0 0 0 8 10 1 0 0 0 0 8 15 1 0 0 0 0 9 18 1 0 0 0 0 10 19 1 0 0 0 0 11 23 1 0 0 0 0 12 24 1 0 0 0 0 13 16 2 0 0 0 0 13 20 1 0 0 0 0 14 17 1 0 0 0 0 14 25 1 0 0 0 0 16 18 1 0 0 0 0 17 21 1 0 0 0 0 17 26 1 6 0 0 0 18 31 1 0 0 0 0 19 23 1 1 0 0 0 19 25 1 0 0 0 0 20 27 2 0 0 0 0 20 31 1 0 0 0 0 21 23 1 1 0 0 0 21 24 1 0 0 0 0 22 24 1 0 0 0 0 22 28 2 0 0 0 0 22 29 1 0 0 0 0 23 3 1 1 0 0 0 24 4 1 1 0 0 0 25 5 1 1 0 0 0 25 30 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	434.27
Volume:	457.482
LogP:	3.569
LogD:	3.287
LogS:	-3.752
# Rotatable Bonds:	6
TPSA:	111.13
# H-Bond Aceptor:	6
# H-Bond Donor:	4
# Rings:	3
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.487
Synthetic Accessibility Score:	4.931
Fsp3:	0.72
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:	-5.489
MDCK Permeability:	1.2274183063709643e-05
Pgp-inhibitor:	0.003
Pgp-substrate:	0.967
Human Intestinal Absorption (HIA):	0.507
20% Bioavailability (F20%):	0.013
30% Bioavailability (F30%):	0.046

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.279
Plasma Protein Binding (PPB):	95.6738510131836%
Volume Distribution (VD):	0.329
Pgp-substrate:	5.802184104919434%

ADMET: Metabolism

CYP1A2-inhibitor:	0.013
CYP1A2-substrate:	0.496
CYP2C19-inhibitor:	0.015
CYP2C19-substrate:	0.496
CYP2C9-inhibitor:	0.131
CYP2C9-substrate:	0.584
CYP2D6-inhibitor:	0.013
CYP2D6-substrate:	0.136
CYP3A4-inhibitor:	0.223
CYP3A4-substrate:	0.073

ADMET: Excretion

Clearance (CL):	2.286
Half-life (T1/2):	0.744

ADMET: Toxicity

hERG Blockers:	0.017
Human Hepatotoxicity (H-HT):	0.218
Drug-inuced Liver Injury (DILI):	0.528
AMES Toxicity:	0.005
Rat Oral Acute Toxicity:	0.032
Maximum Recommended Daily Dose:	0.056
Skin Sensitization:	0.347
Carcinogencity:	0.03
Eye Corrosion:	0.006
Eye Irritation:	0.06
Respiratory Toxicity:	0.576

Download Data

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

Natural Product: NPC476081

Natural Product ID:	NPC476081
*Common Name:**	6Alpha,8Alpha-Dihydroxy-23-Carbossi-Labd-13(14),17-Dien-16,19-Olide
IUPAC Name:	(1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-1,4a,6-trimethyl-5-[(E)-3-methyl-5-(3-methyl-5-oxo-2H-furan-2-yl)pent-3-enyl]-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid
Synonyms:
Standard InCHIKey:	NKTJDMMVKWZHED-YYYYQMEMSA-N
Standard InCHI:	InChI=1S/C25H38O6/c1-15(7-9-18-16(2)13-20(27)31-18)8-10-19-23(3)11-6-12-24(4,22(28)29)21(23)17(26)14-25(19,5)30/h7,13,17-19,21,26,30H,6,8-12,14H2,1-5H3,(H,28,29)/b15-7+/t17-,18?,19+,21+,23+,24+,25+/m0/s1
SMILES:	CC1=CC(=O)OC1CC=C(C)CCC2C3(CCCC(C3C(CC2(C)O)O)(C)C(=O)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL525164
PubChem CID:	44583370
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
NPO33075	salvia dominica	Species	Lamiaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[19459643]

☑ 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
Kd	1

Activity Type	# Activity
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6478	Individual Protein	Tubulin--tyrosine ligase	Homo sapiens	Kd	=	7.0	nM	PMID[490791]

☑ 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 NPC476081 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	204
0.1-0.2	1158
0.2-0.3	3682
0.3-0.4	6364
0.4-0.5	13702
0.5-0.6	7158
0.6-0.7	6528
0.7-0.8	3460
0.8-0.85	368
0.85-0.9	55
0.9-0.95	13
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
0.9688	High Similarity	NPC120321
0.9592	High Similarity	NPC67321
0.9592	High Similarity	NPC187435
0.949	High Similarity	NPC34768
0.9362	High Similarity	NPC276110
0.93	High Similarity	NPC306265
0.92	High Similarity	NPC179380
0.9175	High Similarity	NPC47024
0.9082	High Similarity	NPC471412
0.9062	High Similarity	NPC134072
0.9062	High Similarity	NPC234993
0.901	High Similarity	NPC302788
0.899	High Similarity	NPC165250
0.899	High Similarity	NPC162973
0.898	High Similarity	NPC471413
0.898	High Similarity	NPC38855
0.8947	High Similarity	NPC139692
0.8878	High Similarity	NPC216478
0.8878	High Similarity	NPC278673
0.8854	High Similarity	NPC105490
0.8776	High Similarity	NPC473963
0.8776	High Similarity	NPC175351
0.8776	High Similarity	NPC121402
0.8776	High Similarity	NPC151681
0.8776	High Similarity	NPC224356
0.8776	High Similarity	NPC132753
0.8763	High Similarity	NPC259042
0.8763	High Similarity	NPC157686
0.875	High Similarity	NPC7349
0.8738	High Similarity	NPC275539
0.8738	High Similarity	NPC189075
0.8737	High Similarity	NPC78973
0.8713	High Similarity	NPC112009
0.8713	High Similarity	NPC471208
0.87	High Similarity	NPC303559
0.8673	High Similarity	NPC242848
0.8673	High Similarity	NPC29952
0.8673	High Similarity	NPC473964
0.8673	High Similarity	NPC472363
0.8673	High Similarity	NPC154526
0.8673	High Similarity	NPC472362
0.8673	High Similarity	NPC93245
0.8667	High Similarity	NPC469656
0.8667	High Similarity	NPC469655
0.8667	High Similarity	NPC474846
0.866	High Similarity	NPC24861
0.866	High Similarity	NPC469596
0.866	High Similarity	NPC225474
0.866	High Similarity	NPC57117
0.866	High Similarity	NPC148000
0.8654	High Similarity	NPC284828
0.8654	High Similarity	NPC472216
0.8654	High Similarity	NPC5475
0.8654	High Similarity	NPC173905
0.8646	High Similarity	NPC72845
0.8641	High Similarity	NPC143609
0.8641	High Similarity	NPC110496
0.8632	High Similarity	NPC174342
0.8614	High Similarity	NPC109195
0.8614	High Similarity	NPC469606
0.8614	High Similarity	NPC472552
0.8614	High Similarity	NPC155332
0.8614	High Similarity	NPC475038
0.8614	High Similarity	NPC31058
0.8614	High Similarity	NPC32577
0.8614	High Similarity	NPC114540
0.8614	High Similarity	NPC273005
0.86	High Similarity	NPC476299
0.86	High Similarity	NPC474012
0.8586	High Similarity	NPC51499
0.8586	High Similarity	NPC136781
0.8585	High Similarity	NPC470063
0.8571	High Similarity	NPC183012
0.8558	High Similarity	NPC325054
0.8558	High Similarity	NPC476479
0.8544	High Similarity	NPC111952
0.8544	High Similarity	NPC469607
0.8529	High Similarity	NPC478057
0.8529	High Similarity	NPC180204
0.8529	High Similarity	NPC159533
0.8529	High Similarity	NPC120009
0.8529	High Similarity	NPC45897
0.8529	High Similarity	NPC36688
0.8519	High Similarity	NPC471816
0.8515	High Similarity	NPC472554
0.8515	High Similarity	NPC11974
0.8511	High Similarity	NPC131813
0.8505	High Similarity	NPC25909
0.85	High Similarity	NPC325229
0.85	High Similarity	NPC316598
0.85	High Similarity	NPC275086
0.8485	Intermediate Similarity	NPC165632
0.8485	Intermediate Similarity	NPC284518
0.8485	Intermediate Similarity	NPC202833
0.8476	Intermediate Similarity	NPC474243
0.8454	Intermediate Similarity	NPC186363
0.8454	Intermediate Similarity	NPC233345
0.8438	Intermediate Similarity	NPC194642
0.8431	Intermediate Similarity	NPC58329
0.8431	Intermediate Similarity	NPC295791
0.8431	Intermediate Similarity	NPC137430
0.8416	Intermediate Similarity	NPC117685
0.8416	Intermediate Similarity	NPC324841
0.8416	Intermediate Similarity	NPC251680
0.8416	Intermediate Similarity	NPC470074
0.8416	Intermediate Similarity	NPC16601
0.8416	Intermediate Similarity	NPC476767
0.8416	Intermediate Similarity	NPC201406
0.8411	Intermediate Similarity	NPC269530
0.8411	Intermediate Similarity	NPC12046
0.8411	Intermediate Similarity	NPC277769
0.8411	Intermediate Similarity	NPC4573
0.8411	Intermediate Similarity	NPC194951
0.84	Intermediate Similarity	NPC73911
0.84	Intermediate Similarity	NPC91695
0.84	Intermediate Similarity	NPC70145
0.84	Intermediate Similarity	NPC474343
0.84	Intermediate Similarity	NPC100912
0.8396	Intermediate Similarity	NPC478209
0.8396	Intermediate Similarity	NPC472214
0.8396	Intermediate Similarity	NPC472215
0.8396	Intermediate Similarity	NPC472666
0.8384	Intermediate Similarity	NPC266899
0.8381	Intermediate Similarity	NPC322903
0.8381	Intermediate Similarity	NPC38948
0.8381	Intermediate Similarity	NPC300614
0.8381	Intermediate Similarity	NPC472219
0.8381	Intermediate Similarity	NPC472218
0.8381	Intermediate Similarity	NPC90946
0.8381	Intermediate Similarity	NPC472217
0.8367	Intermediate Similarity	NPC472641
0.8367	Intermediate Similarity	NPC472640
0.8367	Intermediate Similarity	NPC205034
0.8367	Intermediate Similarity	NPC53555
0.8367	Intermediate Similarity	NPC152778
0.8367	Intermediate Similarity	NPC110022
0.8367	Intermediate Similarity	NPC162615
0.8365	Intermediate Similarity	NPC119855
0.8365	Intermediate Similarity	NPC478208
0.8365	Intermediate Similarity	NPC220217
0.8351	Intermediate Similarity	NPC232202
0.8351	Intermediate Similarity	NPC472642
0.8351	Intermediate Similarity	NPC475776
0.835	Intermediate Similarity	NPC476237
0.835	Intermediate Similarity	NPC189588
0.835	Intermediate Similarity	NPC10232
0.835	Intermediate Similarity	NPC471938
0.835	Intermediate Similarity	NPC61442
0.835	Intermediate Similarity	NPC254202
0.835	Intermediate Similarity	NPC187302
0.835	Intermediate Similarity	NPC99266
0.835	Intermediate Similarity	NPC8196
0.835	Intermediate Similarity	NPC222153
0.835	Intermediate Similarity	NPC97487
0.835	Intermediate Similarity	NPC196471
0.835	Intermediate Similarity	NPC23584
0.8349	Intermediate Similarity	NPC471127
0.8349	Intermediate Similarity	NPC469794
0.8349	Intermediate Similarity	NPC154363
0.8349	Intermediate Similarity	NPC234858
0.8349	Intermediate Similarity	NPC72772
0.8333	Intermediate Similarity	NPC477126
0.8333	Intermediate Similarity	NPC474271
0.8333	Intermediate Similarity	NPC475958
0.8333	Intermediate Similarity	NPC104560
0.8333	Intermediate Similarity	NPC471204
0.8333	Intermediate Similarity	NPC157441
0.8333	Intermediate Similarity	NPC93411
0.8333	Intermediate Similarity	NPC235142
0.8333	Intermediate Similarity	NPC115899
0.8317	Intermediate Similarity	NPC222303
0.8317	Intermediate Similarity	NPC108368
0.8317	Intermediate Similarity	NPC473154
0.8317	Intermediate Similarity	NPC107806
0.8317	Intermediate Similarity	NPC72647
0.8317	Intermediate Similarity	NPC57079
0.8317	Intermediate Similarity	NPC476806
0.8317	Intermediate Similarity	NPC119036
0.8317	Intermediate Similarity	NPC476807
0.8317	Intermediate Similarity	NPC218107
0.8317	Intermediate Similarity	NPC478056
0.8316	Intermediate Similarity	NPC185638
0.8302	Intermediate Similarity	NPC31522
0.8302	Intermediate Similarity	NPC273433
0.8302	Intermediate Similarity	NPC475065
0.8302	Intermediate Similarity	NPC206618
0.8302	Intermediate Similarity	NPC42662
0.8302	Intermediate Similarity	NPC299590
0.83	Intermediate Similarity	NPC209297
0.83	Intermediate Similarity	NPC475380
0.83	Intermediate Similarity	NPC16967
0.83	Intermediate Similarity	NPC228766
0.83	Intermediate Similarity	NPC165528
0.8288	Intermediate Similarity	NPC469380
0.8286	Intermediate Similarity	NPC329048
0.8286	Intermediate Similarity	NPC330011
0.8286	Intermediate Similarity	NPC471205
0.8286	Intermediate Similarity	NPC180744
0.8286	Intermediate Similarity	NPC475074
0.8286	Intermediate Similarity	NPC216636

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 NPC476081 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	172
0.1-0.2	1446
0.2-0.3	3418
0.3-0.4	2514
0.4-0.5	1041
0.5-0.6	265
0.6-0.7	204
0.7-0.8	83
0.8-0.85	7
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.85	High Similarity	NPD7638	Approved
0.8416	Intermediate Similarity	NPD7639	Approved
0.8416	Intermediate Similarity	NPD7640	Approved
0.8302	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.8224	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.8137	Intermediate Similarity	NPD4225	Approved
0.8037	Intermediate Similarity	NPD6686	Approved
0.7946	Intermediate Similarity	NPD7115	Discovery
0.7944	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.7895	Intermediate Similarity	NPD4752	Clinical (unspecified phase)
0.7864	Intermediate Similarity	NPD7902	Approved
0.785	Intermediate Similarity	NPD5739	Approved
0.785	Intermediate Similarity	NPD6675	Approved
0.785	Intermediate Similarity	NPD7128	Approved
0.785	Intermediate Similarity	NPD6402	Approved
0.7822	Intermediate Similarity	NPD6399	Phase 3
0.7798	Intermediate Similarity	NPD6373	Approved
0.7798	Intermediate Similarity	NPD6372	Approved
0.7745	Intermediate Similarity	NPD7748	Approved
0.7736	Intermediate Similarity	NPD7632	Discontinued
0.7723	Intermediate Similarity	NPD7515	Phase 2
0.7712	Intermediate Similarity	NPD7507	Approved
0.7706	Intermediate Similarity	NPD6881	Approved
0.7706	Intermediate Similarity	NPD6899	Approved
0.7706	Intermediate Similarity	NPD7320	Approved
0.7667	Intermediate Similarity	NPD7319	Approved
0.7658	Intermediate Similarity	NPD6650	Approved
0.7658	Intermediate Similarity	NPD6649	Approved
0.7615	Intermediate Similarity	NPD5701	Approved
0.7615	Intermediate Similarity	NPD5697	Approved
0.7576	Intermediate Similarity	NPD3618	Phase 1
0.7573	Intermediate Similarity	NPD7901	Clinical (unspecified phase)
0.7573	Intermediate Similarity	NPD7900	Approved
0.7568	Intermediate Similarity	NPD7102	Approved
0.7568	Intermediate Similarity	NPD7290	Approved
0.7568	Intermediate Similarity	NPD6883	Approved
0.7565	Intermediate Similarity	NPD7328	Approved
0.7565	Intermediate Similarity	NPD7327	Approved
0.7545	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7524	Intermediate Similarity	NPD6084	Phase 2
0.7524	Intermediate Similarity	NPD6083	Phase 2
0.7523	Intermediate Similarity	NPD6008	Approved
0.75	Intermediate Similarity	NPD8130	Phase 1
0.75	Intermediate Similarity	NPD7516	Approved
0.75	Intermediate Similarity	NPD6847	Approved
0.75	Intermediate Similarity	NPD6869	Approved
0.75	Intermediate Similarity	NPD6617	Approved
0.7477	Intermediate Similarity	NPD6012	Approved
0.7477	Intermediate Similarity	NPD6014	Approved
0.7477	Intermediate Similarity	NPD6013	Approved
0.7477	Intermediate Similarity	NPD5344	Discontinued
0.7475	Intermediate Similarity	NPD1694	Approved
0.7451	Intermediate Similarity	NPD46	Approved
0.7451	Intermediate Similarity	NPD6698	Approved
0.7434	Intermediate Similarity	NPD8297	Approved
0.7434	Intermediate Similarity	NPD6882	Approved
0.7434	Intermediate Similarity	NPD6053	Discontinued
0.7387	Intermediate Similarity	NPD6011	Approved
0.7379	Intermediate Similarity	NPD8035	Phase 2
0.7379	Intermediate Similarity	NPD7637	Suspended
0.7379	Intermediate Similarity	NPD8034	Phase 2
0.7373	Intermediate Similarity	NPD8378	Approved
0.7373	Intermediate Similarity	NPD8380	Approved
0.7373	Intermediate Similarity	NPD8335	Approved
0.7373	Intermediate Similarity	NPD8033	Approved
0.7373	Intermediate Similarity	NPD8379	Approved
0.7373	Intermediate Similarity	NPD8296	Approved
0.7358	Intermediate Similarity	NPD4755	Approved
0.7353	Intermediate Similarity	NPD5328	Approved
0.7345	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.7308	Intermediate Similarity	NPD5779	Approved
0.7308	Intermediate Similarity	NPD5778	Approved
0.7308	Intermediate Similarity	NPD4202	Approved
0.729	Intermediate Similarity	NPD5696	Approved
0.7288	Intermediate Similarity	NPD8294	Approved
0.7288	Intermediate Similarity	NPD8377	Approved
0.7257	Intermediate Similarity	NPD6371	Approved
0.7248	Intermediate Similarity	NPD5211	Phase 2
0.7228	Intermediate Similarity	NPD5330	Approved
0.7228	Intermediate Similarity	NPD6684	Approved
0.7228	Intermediate Similarity	NPD7334	Approved
0.7228	Intermediate Similarity	NPD7521	Approved
0.7228	Intermediate Similarity	NPD7146	Approved
0.7228	Intermediate Similarity	NPD6409	Approved
0.7222	Intermediate Similarity	NPD5286	Approved
0.7222	Intermediate Similarity	NPD4700	Approved
0.7222	Intermediate Similarity	NPD4696	Approved
0.7222	Intermediate Similarity	NPD5285	Approved
0.7222	Intermediate Similarity	NPD6648	Approved
0.7217	Intermediate Similarity	NPD4632	Approved
0.7212	Intermediate Similarity	NPD6079	Approved
0.72	Intermediate Similarity	NPD7338	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD4786	Approved
0.7172	Intermediate Similarity	NPD3667	Approved
0.717	Intermediate Similarity	NPD5695	Phase 3
0.717	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.717	Intermediate Similarity	NPD6356	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD6412	Phase 2
0.7143	Intermediate Similarity	NPD6319	Approved
0.7129	Intermediate Similarity	NPD7520	Clinical (unspecified phase)
0.7117	Intermediate Similarity	NPD5141	Approved
0.7115	Intermediate Similarity	NPD5785	Approved
0.7103	Intermediate Similarity	NPD4697	Phase 3
0.71	Intermediate Similarity	NPD6695	Phase 3
0.7094	Intermediate Similarity	NPD6274	Approved
0.7091	Intermediate Similarity	NPD4633	Approved
0.7091	Intermediate Similarity	NPD5225	Approved
0.7091	Intermediate Similarity	NPD5226	Approved
0.7091	Intermediate Similarity	NPD5224	Approved
0.7087	Intermediate Similarity	NPD5737	Approved
0.7087	Intermediate Similarity	NPD6903	Approved
0.7087	Intermediate Similarity	NPD6672	Approved
0.7087	Intermediate Similarity	NPD7513	Clinical (unspecified phase)
0.7069	Intermediate Similarity	NPD8133	Approved
0.7059	Intermediate Similarity	NPD7100	Approved
0.7059	Intermediate Similarity	NPD7101	Approved
0.7049	Intermediate Similarity	NPD7492	Approved
0.7048	Intermediate Similarity	NPD6411	Approved
0.7048	Intermediate Similarity	NPD5693	Phase 1
0.7034	Intermediate Similarity	NPD6009	Approved
0.703	Intermediate Similarity	NPD3666	Approved
0.703	Intermediate Similarity	NPD3133	Approved
0.703	Intermediate Similarity	NPD3665	Phase 1
0.703	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.7027	Intermediate Similarity	NPD5174	Approved
0.7027	Intermediate Similarity	NPD5175	Approved
0.7019	Intermediate Similarity	NPD4753	Phase 2
0.7018	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD6059	Approved
0.7	Intermediate Similarity	NPD6054	Approved
0.7	Intermediate Similarity	NPD5223	Approved
0.6992	Remote Similarity	NPD6616	Approved
0.6991	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.699	Remote Similarity	NPD3573	Approved
0.6975	Remote Similarity	NPD6335	Approved
0.697	Remote Similarity	NPD7525	Registered
0.6967	Remote Similarity	NPD8328	Phase 3
0.6967	Remote Similarity	NPD7604	Phase 2
0.6957	Remote Similarity	NPD4634	Approved
0.6944	Remote Similarity	NPD5222	Approved
0.6944	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6944	Remote Similarity	NPD5221	Approved
0.6942	Remote Similarity	NPD6908	Approved
0.6942	Remote Similarity	NPD6909	Approved
0.6942	Remote Similarity	NPD5983	Phase 2
0.6942	Remote Similarity	NPD7503	Approved
0.6935	Remote Similarity	NPD8293	Discontinued
0.6935	Remote Similarity	NPD7078	Approved
0.6916	Remote Similarity	NPD5282	Discontinued
0.6903	Remote Similarity	NPD4767	Approved
0.6903	Remote Similarity	NPD4768	Approved
0.6893	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6891	Remote Similarity	NPD6317	Approved
0.6887	Remote Similarity	NPD5281	Approved
0.6887	Remote Similarity	NPD5284	Approved
0.6885	Remote Similarity	NPD6370	Approved
0.6881	Remote Similarity	NPD5173	Approved
0.688	Remote Similarity	NPD7736	Approved
0.6875	Remote Similarity	NPD4754	Approved
0.6857	Remote Similarity	NPD6051	Approved
0.6857	Remote Similarity	NPD6080	Approved
0.6857	Remote Similarity	NPD6101	Approved
0.6857	Remote Similarity	NPD6904	Approved
0.6857	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6857	Remote Similarity	NPD6673	Approved
0.6855	Remote Similarity	NPD6336	Discontinued
0.6852	Remote Similarity	NPD5210	Approved
0.6852	Remote Similarity	NPD4629	Approved
0.6833	Remote Similarity	NPD6313	Approved
0.6833	Remote Similarity	NPD6314	Approved
0.6827	Remote Similarity	NPD7750	Discontinued
0.6827	Remote Similarity	NPD7524	Approved
0.6818	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6807	Remote Similarity	NPD6868	Approved
0.6803	Remote Similarity	NPD6016	Approved
0.6803	Remote Similarity	NPD6921	Approved
0.6803	Remote Similarity	NPD8513	Phase 3
0.6803	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6803	Remote Similarity	NPD8515	Approved
0.6803	Remote Similarity	NPD8517	Approved
0.6803	Remote Similarity	NPD8516	Approved
0.6803	Remote Similarity	NPD6015	Approved
0.68	Remote Similarity	NPD6930	Phase 2
0.68	Remote Similarity	NPD6931	Approved
0.6792	Remote Similarity	NPD7838	Discovery
0.6783	Remote Similarity	NPD4730	Approved
0.6783	Remote Similarity	NPD4729	Approved
0.6783	Remote Similarity	NPD5128	Approved
0.6768	Remote Similarity	NPD6115	Approved
0.6768	Remote Similarity	NPD6697	Approved
0.6768	Remote Similarity	NPD6118	Approved
0.6768	Remote Similarity	NPD6114	Approved
0.6765	Remote Similarity	NPD7154	Phase 3
0.6759	Remote Similarity	NPD6001	Approved
0.6752	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.675	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6748	Remote Similarity	NPD5988	Approved
0.6731	Remote Similarity	NPD4623	Approved
0.6731	Remote Similarity	NPD4519	Discontinued
0.67	Remote Similarity	NPD7645	Phase 2

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