NPASS Compound

Structure

NPC12695 OpenBabel07101718272D 22 24 0 0 0 0 0 0 0 0999 V2000 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.0000 0.0000 C 0 0 0 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 3.4641 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 3.5000 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 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 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 -1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.0000 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 -1.7321 0.0000 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 -0.8660 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 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 22 1 0 0 0 0 2 4 2 0 0 0 0 2 5 1 0 0 0 0 3 6 2 0 0 0 0 3 7 1 0 0 0 0 4 8 1 0 0 0 0 5 9 2 0 0 0 0 6 10 1 0 0 0 0 7 11 2 0 0 0 0 8 13 2 0 0 0 0 9 13 1 0 0 0 0 10 14 2 0 0 0 0 11 14 1 0 0 0 0 12 15 2 0 0 0 0 12 16 1 0 0 0 0 13 15 1 0 0 0 0 14 17 1 0 0 0 0 15 18 1 0 0 0 0 16 17 1 0 0 0 0 16 20 2 0 0 0 0 17 19 2 0 0 0 0 18 19 1 0 0 0 0 18 21 2 0 0 0 0 19 22 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	290.09
Volume:	311.517
LogP:	3.365
LogD:	3.311
LogS:	-4.999
# Rotatable Bonds:	3
TPSA:	43.37
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.815
Synthetic Accessibility Score:	2.198
Fsp3:	0.053
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.718
MDCK Permeability:	1.3311369912116788e-05
Pgp-inhibitor:	0.917
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.02
30% Bioavailability (F30%):	0.047

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006
Plasma Protein Binding (PPB):	100.23164367675781%
Volume Distribution (VD):	0.56
Pgp-substrate:	0.6152867078781128%

ADMET: Metabolism

CYP1A2-inhibitor:	0.974
CYP1A2-substrate:	0.76
CYP2C19-inhibitor:	0.971
CYP2C19-substrate:	0.125
CYP2C9-inhibitor:	0.939
CYP2C9-substrate:	0.569
CYP2D6-inhibitor:	0.676
CYP2D6-substrate:	0.022
CYP3A4-inhibitor:	0.63
CYP3A4-substrate:	0.141

ADMET: Excretion

Clearance (CL):	3.107
Half-life (T1/2):	0.138

ADMET: Toxicity

hERG Blockers:	0.138
Human Hepatotoxicity (H-HT):	0.777
Drug-inuced Liver Injury (DILI):	0.969
AMES Toxicity:	0.141
Rat Oral Acute Toxicity:	0.569
Maximum Recommended Daily Dose:	0.922
Skin Sensitization:	0.342
Carcinogencity:	0.66
Eye Corrosion:	0.003
Eye Irritation:	0.116
Respiratory Toxicity:	0.264

Download Data

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

Natural Product: NPC12695

Natural Product ID:	NPC12695
*Common Name:**	Betulinan C
IUPAC Name:	3-methoxy-2,5-diphenylcyclohexa-2,5-diene-1,4-dione
Synonyms:	Betulinan C
Standard InCHIKey:	RPHQALSHGDIMKF-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C19H14O3/c1-22-19-17(14-10-6-3-7-11-14)16(20)12-15(18(19)21)13-8-4-2-5-9-13/h2-12H,1H3
SMILES:	COC1=C(c2ccccc2)C(=O)C=C(c2ccccc2)C1=O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2331809
PubChem CID:	71657973
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000118] Ketones [CHEMONTID:0003487] Cyclic ketones [CHEMONTID:0002495] Quinones [CHEMONTID:0002384] Benzoquinones [CHEMONTID:0002494] P-benzoquinones

*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
NPO33224	msx 47445	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[23301853]
NPO41065	Floricola striata	Species	Teichosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27557136]
NPO41065	Floricola striata	Species	Teichosporaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30137985]

☑ 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	1
MIC	1
Others	1

Activity Type	# Activity
Individual Protein	1
NON-MOLECULAR	1
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4735	Individual Protein	Phosphodiesterase 4B	Homo sapiens	IC50	=	17000.0	nM	PMID[509980]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	25.0	ug.mL-1	PMID[509980]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	MIC80	>	128.0	ug.mL-1	PMID[509981]

☑ 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 NPC12695 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	229
0.1-0.2	1406
0.2-0.3	3705
0.3-0.4	12109
0.4-0.5	12523
0.5-0.6	10867
0.6-0.7	1590
0.7-0.8	240
0.8-0.85	18
0.85-0.9	7
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.967	High Similarity	NPC103048
0.9333	High Similarity	NPC476484
0.8947	High Similarity	NPC145052
0.8925	High Similarity	NPC34243
0.8804	High Similarity	NPC110420
0.8804	High Similarity	NPC67585
0.8804	High Similarity	NPC303967
0.88	High Similarity	NPC203732
0.8763	High Similarity	NPC112552
0.8476	Intermediate Similarity	NPC67377
0.8469	Intermediate Similarity	NPC476042
0.8302	Intermediate Similarity	NPC326664
0.8252	Intermediate Similarity	NPC470007
0.8252	Intermediate Similarity	NPC470391
0.8224	Intermediate Similarity	NPC474408
0.819	Intermediate Similarity	NPC137315
0.8173	Intermediate Similarity	NPC192577
0.8105	Intermediate Similarity	NPC231591
0.8058	Intermediate Similarity	NPC134120
0.8019	Intermediate Similarity	NPC291799
0.8	Intermediate Similarity	NPC139901
0.8	Intermediate Similarity	NPC477704
0.8	Intermediate Similarity	NPC477693
0.8	Intermediate Similarity	NPC151405
0.7941	Intermediate Similarity	NPC244427
0.7941	Intermediate Similarity	NPC222390
0.7917	Intermediate Similarity	NPC9822
0.7912	Intermediate Similarity	NPC71664
0.79	Intermediate Similarity	NPC156021
0.79	Intermediate Similarity	NPC289201
0.7895	Intermediate Similarity	NPC69057
0.7864	Intermediate Similarity	NPC274443
0.7849	Intermediate Similarity	NPC288903
0.7849	Intermediate Similarity	NPC273758
0.7835	Intermediate Similarity	NPC108026
0.7826	Intermediate Similarity	NPC12936
0.7826	Intermediate Similarity	NPC273033
0.7802	Intermediate Similarity	NPC300205
0.7798	Intermediate Similarity	NPC241851
0.7788	Intermediate Similarity	NPC249067
0.7778	Intermediate Similarity	NPC186128
0.7755	Intermediate Similarity	NPC110704
0.7727	Intermediate Similarity	NPC470764
0.7727	Intermediate Similarity	NPC472164
0.7723	Intermediate Similarity	NPC270654
0.7717	Intermediate Similarity	NPC95868
0.7717	Intermediate Similarity	NPC164086
0.7714	Intermediate Similarity	NPC172483
0.77	Intermediate Similarity	NPC5472
0.7692	Intermediate Similarity	NPC2785
0.7692	Intermediate Similarity	NPC36342
0.7692	Intermediate Similarity	NPC329556
0.7692	Intermediate Similarity	NPC285470
0.7685	Intermediate Similarity	NPC21162
0.7684	Intermediate Similarity	NPC294134
0.7684	Intermediate Similarity	NPC95965
0.7684	Intermediate Similarity	NPC123476
0.7664	Intermediate Similarity	NPC281604
0.7619	Intermediate Similarity	NPC269644
0.7611	Intermediate Similarity	NPC318173
0.7609	Intermediate Similarity	NPC272260
0.7589	Intermediate Similarity	NPC325646
0.7589	Intermediate Similarity	NPC28951
0.7582	Intermediate Similarity	NPC245966
0.7582	Intermediate Similarity	NPC179726
0.7582	Intermediate Similarity	NPC9796
0.7576	Intermediate Similarity	NPC187725
0.7576	Intermediate Similarity	NPC141607
0.7573	Intermediate Similarity	NPC474308
0.7551	Intermediate Similarity	NPC418308
0.7549	Intermediate Similarity	NPC240042
0.7549	Intermediate Similarity	NPC278228
0.7545	Intermediate Similarity	NPC143768
0.7545	Intermediate Similarity	NPC161611
0.7528	Intermediate Similarity	NPC285679
0.7527	Intermediate Similarity	NPC190567
0.7526	Intermediate Similarity	NPC43945
0.7525	Intermediate Similarity	NPC473347
0.7522	Intermediate Similarity	NPC471553
0.75	Intermediate Similarity	NPC40178
0.75	Intermediate Similarity	NPC42211
0.7477	Intermediate Similarity	NPC196075
0.7477	Intermediate Similarity	NPC100767
0.7476	Intermediate Similarity	NPC49994
0.7476	Intermediate Similarity	NPC179411
0.7476	Intermediate Similarity	NPC476120
0.7475	Intermediate Similarity	NPC19256
0.7474	Intermediate Similarity	NPC215008
0.7455	Intermediate Similarity	NPC212415
0.7455	Intermediate Similarity	NPC292834
0.7449	Intermediate Similarity	NPC157778
0.7449	Intermediate Similarity	NPC267262
0.7447	Intermediate Similarity	NPC145053
0.7447	Intermediate Similarity	NPC73978
0.7426	Intermediate Similarity	NPC261181
0.7426	Intermediate Similarity	NPC289883
0.7417	Intermediate Similarity	NPC478165
0.7417	Intermediate Similarity	NPC478162
0.7416	Intermediate Similarity	NPC74458
0.7414	Intermediate Similarity	NPC144547
0.7411	Intermediate Similarity	NPC228936
0.7407	Intermediate Similarity	NPC47536
0.7407	Intermediate Similarity	NPC156648
0.7404	Intermediate Similarity	NPC54647
0.7404	Intermediate Similarity	NPC118343
0.74	Intermediate Similarity	NPC284475
0.7387	Intermediate Similarity	NPC13784
0.7387	Intermediate Similarity	NPC469547
0.7383	Intermediate Similarity	NPC474307
0.7383	Intermediate Similarity	NPC209632
0.7379	Intermediate Similarity	NPC239185
0.7373	Intermediate Similarity	NPC318067
0.7368	Intermediate Similarity	NPC80605
0.7368	Intermediate Similarity	NPC323440
0.7368	Intermediate Similarity	NPC61651
0.7368	Intermediate Similarity	NPC469954
0.7368	Intermediate Similarity	NPC222968
0.7358	Intermediate Similarity	NPC301943
0.7358	Intermediate Similarity	NPC247976
0.7358	Intermediate Similarity	NPC474365
0.7353	Intermediate Similarity	NPC130398
0.7353	Intermediate Similarity	NPC260233
0.7353	Intermediate Similarity	NPC206764
0.7353	Intermediate Similarity	NPC472880
0.7347	Intermediate Similarity	NPC194326
0.7347	Intermediate Similarity	NPC96625
0.7345	Intermediate Similarity	NPC260886
0.7345	Intermediate Similarity	NPC62138
0.7339	Intermediate Similarity	NPC475282
0.7328	Intermediate Similarity	NPC988
0.7328	Intermediate Similarity	NPC105709
0.7328	Intermediate Similarity	NPC289432
0.7328	Intermediate Similarity	NPC232958
0.7327	Intermediate Similarity	NPC153885
0.7327	Intermediate Similarity	NPC77273
0.7327	Intermediate Similarity	NPC188844
0.7327	Intermediate Similarity	NPC1682
0.7327	Intermediate Similarity	NPC59677
0.7327	Intermediate Similarity	NPC155232
0.7321	Intermediate Similarity	NPC477411
0.7321	Intermediate Similarity	NPC11824
0.732	Intermediate Similarity	NPC475710
0.7315	Intermediate Similarity	NPC69332
0.7315	Intermediate Similarity	NPC29989
0.7315	Intermediate Similarity	NPC95178
0.7312	Intermediate Similarity	NPC76455
0.7312	Intermediate Similarity	NPC137847
0.7311	Intermediate Similarity	NPC295664
0.7308	Intermediate Similarity	NPC317280
0.7308	Intermediate Similarity	NPC329387
0.7308	Intermediate Similarity	NPC134882
0.7304	Intermediate Similarity	NPC152159
0.73	Intermediate Similarity	NPC213156
0.73	Intermediate Similarity	NPC277277
0.73	Intermediate Similarity	NPC240108
0.73	Intermediate Similarity	NPC173413
0.7297	Intermediate Similarity	NPC280789
0.7297	Intermediate Similarity	NPC218855
0.7292	Intermediate Similarity	NPC285773
0.729	Intermediate Similarity	NPC329282
0.729	Intermediate Similarity	NPC114594
0.7288	Intermediate Similarity	NPC164947
0.7288	Intermediate Similarity	NPC65627
0.7281	Intermediate Similarity	NPC108532
0.7281	Intermediate Similarity	NPC19290
0.7281	Intermediate Similarity	NPC469843
0.7255	Intermediate Similarity	NPC238219
0.7248	Intermediate Similarity	NPC141523
0.7241	Intermediate Similarity	NPC204784
0.7238	Intermediate Similarity	NPC325497
0.7238	Intermediate Similarity	NPC7435
0.7232	Intermediate Similarity	NPC470253
0.7232	Intermediate Similarity	NPC471481
0.7228	Intermediate Similarity	NPC133461
0.7228	Intermediate Similarity	NPC317645
0.7227	Intermediate Similarity	NPC328107
0.7227	Intermediate Similarity	NPC473942
0.7227	Intermediate Similarity	NPC135062
0.7222	Intermediate Similarity	NPC269457
0.7217	Intermediate Similarity	NPC268930
0.7212	Intermediate Similarity	NPC276775
0.7212	Intermediate Similarity	NPC92754
0.7212	Intermediate Similarity	NPC265220
0.7212	Intermediate Similarity	NPC249912
0.7207	Intermediate Similarity	NPC265513
0.7207	Intermediate Similarity	NPC474157
0.7204	Intermediate Similarity	NPC329318
0.72	Intermediate Similarity	NPC113307
0.7196	Intermediate Similarity	NPC60679
0.7193	Intermediate Similarity	NPC226093
0.7193	Intermediate Similarity	NPC23402
0.7193	Intermediate Similarity	NPC135730
0.7193	Intermediate Similarity	NPC471616
0.7191	Intermediate Similarity	NPC98880
0.7188	Intermediate Similarity	NPC323103
0.7182	Intermediate Similarity	NPC474364
0.7182	Intermediate Similarity	NPC269023
0.7182	Intermediate Similarity	NPC99846
0.7179	Intermediate Similarity	NPC476225
0.7179	Intermediate Similarity	NPC473243

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 NPC12695 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	223
0.1-0.2	986
0.2-0.3	1067
0.3-0.4	3165
0.4-0.5	2441
0.5-0.6	1053
0.6-0.7	175
0.7-0.8	40
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
0.7826	Intermediate Similarity	NPD942	Approved
0.7788	Intermediate Similarity	NPD1237	Approved
0.7745	Intermediate Similarity	NPD2066	Phase 3
0.7717	Intermediate Similarity	NPD1507	Clinical (unspecified phase)
0.7692	Intermediate Similarity	NPD1929	Approved
0.7692	Intermediate Similarity	NPD1930	Approved
0.7692	Intermediate Similarity	NPD1931	Clinical (unspecified phase)
0.7624	Intermediate Similarity	NPD1989	Approved
0.7619	Intermediate Similarity	NPD5909	Discontinued
0.76	Intermediate Similarity	NPD5122	Clinical (unspecified phase)
0.7526	Intermediate Similarity	NPD650	Approved
0.7455	Intermediate Similarity	NPD1609	Clinical (unspecified phase)
0.7431	Intermediate Similarity	NPD2067	Discontinued
0.7429	Intermediate Similarity	NPD1932	Approved
0.7426	Intermediate Similarity	NPD1202	Approved
0.7419	Intermediate Similarity	NPD9490	Approved
0.7404	Intermediate Similarity	NPD1238	Approved
0.74	Intermediate Similarity	NPD7609	Phase 3
0.7379	Intermediate Similarity	NPD3495	Discontinued
0.7327	Intermediate Similarity	NPD7631	Approved
0.7321	Intermediate Similarity	NPD1241	Discontinued
0.7312	Intermediate Similarity	NPD225	Approved
0.7312	Intermediate Similarity	NPD227	Approved
0.7292	Intermediate Similarity	NPD9491	Approved
0.7257	Intermediate Similarity	NPD690	Clinical (unspecified phase)
0.7255	Intermediate Similarity	NPD1563	Approved
0.7238	Intermediate Similarity	NPD7798	Approved
0.7228	Intermediate Similarity	NPD1239	Approved
0.7182	Intermediate Similarity	NPD2329	Discontinued
0.7172	Intermediate Similarity	NPD1087	Approved
0.7157	Intermediate Similarity	NPD1508	Approved
0.7129	Intermediate Similarity	NPD3673	Approved
0.7129	Intermediate Similarity	NPD3672	Approved
0.7119	Intermediate Similarity	NPD4879	Approved
0.7083	Intermediate Similarity	NPD226	Approved
0.708	Intermediate Similarity	NPD7094	Approved
0.708	Intermediate Similarity	NPD6858	Approved
0.7071	Intermediate Similarity	NPD9257	Approved
0.7071	Intermediate Similarity	NPD9259	Approved
0.7054	Intermediate Similarity	NPD4141	Clinical (unspecified phase)
0.7048	Intermediate Similarity	NPD1565	Approved
0.7048	Intermediate Similarity	NPD1566	Phase 3
0.7048	Intermediate Similarity	NPD1564	Approved
0.7034	Intermediate Similarity	NPD3412	Clinical (unspecified phase)
0.703	Intermediate Similarity	NPD800	Approved
0.7019	Intermediate Similarity	NPD688	Clinical (unspecified phase)
0.7019	Intermediate Similarity	NPD1693	Approved
0.7009	Intermediate Similarity	NPD3135	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD3972	Approved
0.7	Intermediate Similarity	NPD506	Clinical (unspecified phase)
0.6981	Remote Similarity	NPD9495	Approved
0.6975	Remote Similarity	NPD7457	Clinical (unspecified phase)
0.6972	Remote Similarity	NPD164	Approved
0.6961	Remote Similarity	NPD1090	Approved
0.6961	Remote Similarity	NPD1089	Approved
0.6961	Remote Similarity	NPD1086	Approved
0.6952	Remote Similarity	NPD1843	Approved
0.6917	Remote Similarity	NPD1547	Clinical (unspecified phase)
0.6911	Remote Similarity	NPD2788	Approved
0.6903	Remote Similarity	NPD2181	Clinical (unspecified phase)
0.6885	Remote Similarity	NPD1876	Approved
0.6881	Remote Similarity	NPD6647	Phase 2
0.6875	Remote Similarity	NPD6831	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD2182	Approved
0.6863	Remote Similarity	NPD5346	Phase 2
0.6863	Remote Similarity	NPD5347	Phase 2
0.6832	Remote Similarity	NPD4793	Discontinued
0.6832	Remote Similarity	NPD1282	Approved
0.6827	Remote Similarity	NPD1088	Approved
0.681	Remote Similarity	NPD5951	Approved
0.681	Remote Similarity	NPD2629	Approved
0.6796	Remote Similarity	NPD9256	Approved
0.6796	Remote Similarity	NPD9258	Approved
0.6792	Remote Similarity	NPD5206	Clinical (unspecified phase)
0.6777	Remote Similarity	NPD6287	Discontinued
0.6774	Remote Similarity	NPD2798	Approved
0.6723	Remote Similarity	NPD7009	Phase 2
0.6721	Remote Similarity	NPD4878	Approved
0.6698	Remote Similarity	NPD4094	Approved
0.6695	Remote Similarity	NPD4576	Approved
0.6695	Remote Similarity	NPD4574	Approved
0.6667	Remote Similarity	NPD5157	Phase 1
0.6667	Remote Similarity	NPD5159	Phase 2
0.6667	Remote Similarity	NPD5158	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD5926	Approved
0.6667	Remote Similarity	NPD3646	Clinical (unspecified phase)
0.6639	Remote Similarity	NPD2347	Approved
0.6639	Remote Similarity	NPD7610	Discontinued
0.6613	Remote Similarity	NPD5667	Approved
0.6612	Remote Similarity	NPD2345	Approved
0.6612	Remote Similarity	NPD7163	Clinical (unspecified phase)
0.6607	Remote Similarity	NPD5048	Discontinued
0.6574	Remote Similarity	NPD4655	Approved
0.6574	Remote Similarity	NPD4657	Approved
0.656	Remote Similarity	NPD3266	Approved
0.656	Remote Similarity	NPD3267	Approved
0.6557	Remote Similarity	NPD4136	Approved
0.6557	Remote Similarity	NPD4135	Approved
0.6557	Remote Similarity	NPD4106	Approved
0.6542	Remote Similarity	NPD9260	Approved
0.6535	Remote Similarity	NPD6832	Phase 2
0.6529	Remote Similarity	NPD1651	Approved
0.6529	Remote Similarity	NPD4102	Approved
0.6529	Remote Similarity	NPD4105	Approved
0.6525	Remote Similarity	NPD1246	Approved
0.6522	Remote Similarity	NPD1317	Discontinued
0.6512	Remote Similarity	NPD7961	Discontinued
0.65	Remote Similarity	NPD5536	Phase 2
0.6496	Remote Similarity	NPD2607	Approved
0.6486	Remote Similarity	NPD6024	Approved
0.6486	Remote Similarity	NPD2648	Phase 3
0.6486	Remote Similarity	NPD6027	Approved
0.6486	Remote Similarity	NPD2193	Phase 2
0.6486	Remote Similarity	NPD2171	Approved
0.6484	Remote Similarity	NPD6108	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD6039	Approved
0.6475	Remote Similarity	NPD5305	Approved
0.6475	Remote Similarity	NPD5306	Approved
0.6446	Remote Similarity	NPD1894	Discontinued
0.6436	Remote Similarity	NPD3971	Phase 1
0.6434	Remote Similarity	NPD6798	Discontinued
0.6434	Remote Similarity	NPD2313	Discontinued
0.6429	Remote Similarity	NPD2797	Approved
0.6429	Remote Similarity	NPD9261	Approved
0.6422	Remote Similarity	NPD1099	Approved
0.6422	Remote Similarity	NPD1100	Approved
0.6418	Remote Similarity	NPD2353	Approved
0.6418	Remote Similarity	NPD2355	Clinical (unspecified phase)
0.6417	Remote Similarity	NPD405	Clinical (unspecified phase)
0.6417	Remote Similarity	NPD9493	Approved
0.6389	Remote Similarity	NPD2934	Approved
0.6389	Remote Similarity	NPD2933	Approved
0.6385	Remote Similarity	NPD7713	Phase 3
0.6385	Remote Similarity	NPD6233	Phase 2
0.6379	Remote Similarity	NPD4233	Approved
0.6379	Remote Similarity	NPD4234	Approved
0.6379	Remote Similarity	NPD1756	Approved
0.6379	Remote Similarity	NPD1752	Approved
0.6378	Remote Similarity	NPD6007	Clinical (unspecified phase)
0.6371	Remote Similarity	NPD1281	Approved
0.6371	Remote Similarity	NPD4807	Approved
0.6371	Remote Similarity	NPD1201	Approved
0.6371	Remote Similarity	NPD4806	Approved
0.6357	Remote Similarity	NPD5952	Clinical (unspecified phase)
0.6357	Remote Similarity	NPD7008	Discontinued
0.635	Remote Similarity	NPD3887	Approved
0.6343	Remote Similarity	NPD2796	Approved
0.6341	Remote Similarity	NPD2932	Approved
0.6341	Remote Similarity	NPD17	Approved
0.6339	Remote Similarity	NPD2196	Discontinued
0.6336	Remote Similarity	NPD1240	Approved
0.6336	Remote Similarity	NPD4307	Phase 2
0.6333	Remote Similarity	NPD3317	Approved
0.6333	Remote Similarity	NPD4198	Discontinued
0.633	Remote Similarity	NPD2859	Approved
0.633	Remote Similarity	NPD2860	Approved
0.6311	Remote Similarity	NPD9545	Approved
0.6308	Remote Similarity	NPD3268	Approved
0.6303	Remote Similarity	NPD2652	Approved
0.6303	Remote Similarity	NPD2650	Approved
0.6299	Remote Similarity	NPD1470	Approved
0.6296	Remote Similarity	NPD1471	Phase 3
0.6289	Remote Similarity	NPD9716	Approved
0.6288	Remote Similarity	NPD1933	Approved
0.6283	Remote Similarity	NPD3357	Discontinued
0.6279	Remote Similarity	NPD5201	Approved
0.6279	Remote Similarity	NPD5203	Approved
0.6279	Remote Similarity	NPD4617	Approved
0.6279	Remote Similarity	NPD5202	Clinical (unspecified phase)
0.6279	Remote Similarity	NPD4620	Approved
0.6269	Remote Similarity	NPD3748	Approved
0.6261	Remote Similarity	NPD3134	Approved
0.6261	Remote Similarity	NPD5706	Approved
0.6261	Remote Similarity	NPD5705	Approved
0.6261	Remote Similarity	NPD5704	Approved
0.626	Remote Similarity	NPD1245	Approved
0.626	Remote Similarity	NPD3025	Approved
0.626	Remote Similarity	NPD3024	Approved
0.626	Remote Similarity	NPD4196	Clinical (unspecified phase)
0.626	Remote Similarity	NPD4062	Phase 3
0.6259	Remote Similarity	NPD6799	Approved
0.625	Remote Similarity	NPD4980	Approved
0.6241	Remote Similarity	NPD1607	Approved
0.624	Remote Similarity	NPD7436	Approved
0.624	Remote Similarity	NPD7437	Approved
0.6239	Remote Similarity	NPD5451	Approved
0.6232	Remote Similarity	NPD2354	Approved
0.623	Remote Similarity	NPD6065	Approved
0.6228	Remote Similarity	NPD2577	Clinical (unspecified phase)
0.622	Remote Similarity	NPD2199	Approved
0.622	Remote Similarity	NPD2198	Approved
0.622	Remote Similarity	NPD1283	Approved
0.6218	Remote Similarity	NPD1279	Clinical (unspecified phase)
0.6218	Remote Similarity	NPD5535	Approved
0.6218	Remote Similarity	NPD5277	Phase 2
0.6214	Remote Similarity	NPD5401	Approved
0.6212	Remote Similarity	NPD3142	Approved
0.6212	Remote Similarity	NPD3140	Approved
0.621	Remote Similarity	NPD3019	Approved
0.6207	Remote Similarity	NPD9267	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