NPASS Compound

Structure

CID163004 OpenBabel06191715532D 26 29 0 0 1 0 0 0 0 0999 V2000 5.2521 1.0163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5903 -0.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7319 0.0259 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7169 1.0258 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4921 0.7376 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7541 2.4778 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4412 3.1110 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0938 4.1369 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3011 1.3254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7319 -0.0259 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4452 3.2006 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8884 1.4869 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6831 1.3254 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0150 0.9999 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9921 2.2764 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8584 -0.5129 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8584 0.5129 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9921 2.2764 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7468 0.9740 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 0.1073 4.3007 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5799 3.0854 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8435 -1.5128 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2232 2.9158 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3265 1.8813 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0150 -0.9999 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 9 1 0 0 0 0 2 10 1 0 0 0 0 3 17 1 0 0 0 0 4 17 1 0 0 0 0 5 9 2 0 0 0 0 5 13 1 0 0 0 0 6 11 2 0 0 0 0 6 12 1 0 0 0 0 7 11 1 0 0 0 0 7 18 1 0 0 0 0 8 11 1 0 0 0 0 8 21 1 0 0 0 0 9 15 1 0 0 0 0 10 16 1 0 0 0 0 10 19 1 6 0 0 0 12 14 1 0 0 0 0 12 19 1 6 0 0 0 13 18 1 1 0 0 0 13 19 1 0 0 0 0 14 17 1 0 0 0 0 14 20 1 1 0 0 0 15 18 1 0 0 0 0 15 22 2 0 0 0 0 16 20 1 1 0 0 0 16 23 1 0 0 0 0 17 20 1 0 0 0 0 18 24 1 1 0 0 0 19 25 1 6 0 0 0 20 26 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	364.19
Volume:	365.082
LogP:	1.238
LogD:	0.707
LogS:	-3.172
# Rotatable Bonds:	1
TPSA:	118.22
# H-Bond Aceptor:	6
# H-Bond Donor:	5
# Rings:	4
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.416
Synthetic Accessibility Score:	5.18
Fsp3:	0.75
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.207
MDCK Permeability:	9.848499030340463e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.269
Human Intestinal Absorption (HIA):	0.078
20% Bioavailability (F20%):	0.772
30% Bioavailability (F30%):	0.012

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.294
Plasma Protein Binding (PPB):	33.447547912597656%
Volume Distribution (VD):	0.598
Pgp-substrate:	51.051963806152344%

ADMET: Metabolism

CYP1A2-inhibitor:	0.026
CYP1A2-substrate:	0.252
CYP2C19-inhibitor:	0.016
CYP2C19-substrate:	0.606
CYP2C9-inhibitor:	0.004
CYP2C9-substrate:	0.085
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.11
CYP3A4-inhibitor:	0.021
CYP3A4-substrate:	0.17

ADMET: Excretion

Clearance (CL):	1.54
Half-life (T1/2):	0.539

ADMET: Toxicity

hERG Blockers:	0.086
Human Hepatotoxicity (H-HT):	0.557
Drug-inuced Liver Injury (DILI):	0.118
AMES Toxicity:	0.075
Rat Oral Acute Toxicity:	0.885
Maximum Recommended Daily Dose:	0.759
Skin Sensitization:	0.342
Carcinogencity:	0.082
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.976

Download Data

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

Natural Product: NPC163004

Natural Product ID:	NPC163004
*Common Name:**	Phorbol
IUPAC Name:	n.a.
Synonyms:	Phorbol
Standard InCHIKey:	QGVLYPPODPLXMB-UBTYZVCOSA-N
Standard InCHI:	InChI=1S/C20H28O6/c1-9-5-13-18(24,15(9)22)7-11(8-21)6-12-14-17(3,4)20(14,26)16(23)10(2)19(12,13)25/h5-6,10,12-14,16,21,23-26H,7-8H2,1-4H3/t10-,12+,13-,14-,16-,18-,19-,20-/m1/s1
SMILES:	CC1=C[C@@H]2[C@](CC(=C[C@H]3[C@@H]4C(C)(C)[C@@]4([C@@H]([C@@H](C)[C@]23O)O)O)CO)(C1=O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL124518
PubChem CID:	442070
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002875] Tigliane and ingenane diterpenoids

*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
NPO8899	Synapta maculata	Species	Synaptidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18290630]
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	Eukaryota	n.a.	twig	n.a.	PMID[21520897]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	Roots	n.a.	n.a.	PMID[22916954]
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	Eukaryota	Stems	n.a.	n.a.	PMID[23148674]
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23215460]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12368	Vallesia dichotoma	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1137	Pseudophegopteris bukoensis	Species	Thelypteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8899	Synapta maculata	Species	Synaptidae	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
EC50	6
IC50	4
Others	6

Activity Type	# Activity
Cell Line	5
NON-MOLECULAR	2
Organism	5
Others	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT517	Cell Line	Panel NCI-60 (60 carcinoma cell lines)	Homo sapiens	Log 1/GI50	=	4.3	n.a.	PMID[518291]
NPT189	Cell Line	Vero	Chlorocebus aethiops	CC50	>	343000.0	nM	PMID[518292]
NPT1229	Cell Line	Huh-7	Homo sapiens	IC50	=	5930.0	nM	PMID[518294]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	15300.0	nM	PMID[518294]
NPT111	Cell Line	K562	Homo sapiens	IC50	=	100.0	nM	PMID[518294]
NPT856	Organism	Semliki forest virus	Semliki forest virus	EC50	>	274000.0	nM	PMID[518292]
NPT338	Organism	Sindbis virus	Sindbis virus	EC50	>	274000.0	nM	PMID[518292]
NPT2	Others	Unspecified		Ratio CC50/EC50	>	1.0	n.a.	PMID[518292]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	EC50	>	343000.0	nM	PMID[518292]
NPT332	Organism	Human immunodeficiency virus type 2 (ISOLATE ROD)	Human immunodeficiency virus type 2 (ISOLATE ROD)	EC50	>	343000.0	nM	PMID[518293]
NPT2	Others	Unspecified		Ratio CC50/EC50	>	1.0	n.a.	PMID[518293]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	EC50	>	343000.0	nM	PMID[518293]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	>	343000.0	nM	PMID[518293]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	IC50	>	30000.0	nM	PMID[518294]

☑ 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 NPC163004 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	224
0.1-0.2	1439
0.2-0.3	4803
0.3-0.4	8421
0.4-0.5	14023
0.5-0.6	8385
0.6-0.7	4640
0.7-0.8	635
0.8-0.85	35
0.85-0.9	71
0.9-0.95	20
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9346	High Similarity	NPC156252
0.9083	High Similarity	NPC171905
0.9083	High Similarity	NPC471125
0.9083	High Similarity	NPC472397
0.9083	High Similarity	NPC472758
0.9	High Similarity	NPC22628
0.9	High Similarity	NPC275696
0.9	High Similarity	NPC255081
0.9	High Similarity	NPC5991
0.9	High Similarity	NPC5989
0.9	High Similarity	NPC471108
0.8981	High Similarity	NPC472400
0.8962	High Similarity	NPC153036
0.8919	High Similarity	NPC145182
0.8919	High Similarity	NPC157252
0.8919	High Similarity	NPC471126
0.8919	High Similarity	NPC471128
0.8889	High Similarity	NPC472757
0.8879	High Similarity	NPC475937
0.8879	High Similarity	NPC158523
0.8839	High Similarity	NPC472401
0.8839	High Similarity	NPC52839
0.8761	High Similarity	NPC19464
0.8761	High Similarity	NPC162009
0.8761	High Similarity	NPC257017
0.8727	High Similarity	NPC234858
0.8727	High Similarity	NPC471127
0.8727	High Similarity	NPC154363
0.8716	High Similarity	NPC477091
0.8716	High Similarity	NPC71889
0.8684	High Similarity	NPC472399
0.8649	High Similarity	NPC10721
0.8636	High Similarity	NPC474872
0.8609	High Similarity	NPC145238
0.8584	High Similarity	NPC475885
0.8571	High Similarity	NPC146280
0.8571	High Similarity	NPC124676
0.8545	High Similarity	NPC73300
0.8545	High Similarity	NPC108721
0.8532	High Similarity	NPC96739
0.8532	High Similarity	NPC174471
0.8532	High Similarity	NPC474871
0.8532	High Similarity	NPC260786
0.8496	Intermediate Similarity	NPC236918
0.8496	Intermediate Similarity	NPC156745
0.8482	Intermediate Similarity	NPC153651
0.8455	Intermediate Similarity	NPC101825
0.8455	Intermediate Similarity	NPC89227
0.8455	Intermediate Similarity	NPC475391
0.8455	Intermediate Similarity	NPC221511
0.8455	Intermediate Similarity	NPC215643
0.8455	Intermediate Similarity	NPC170212
0.8455	Intermediate Similarity	NPC17138
0.8455	Intermediate Similarity	NPC265499
0.8455	Intermediate Similarity	NPC151216
0.8421	Intermediate Similarity	NPC472759
0.8421	Intermediate Similarity	NPC329080
0.8421	Intermediate Similarity	NPC19336
0.8421	Intermediate Similarity	NPC185876
0.8407	Intermediate Similarity	NPC472760
0.839	Intermediate Similarity	NPC270109
0.8378	Intermediate Similarity	NPC474937
0.8333	Intermediate Similarity	NPC180640
0.8318	Intermediate Similarity	NPC72255
0.8257	Intermediate Similarity	NPC217201
0.8257	Intermediate Similarity	NPC65941
0.822	Intermediate Similarity	NPC222307
0.8182	Intermediate Similarity	NPC214644
0.8182	Intermediate Similarity	NPC11710
0.8165	Intermediate Similarity	NPC477916
0.8165	Intermediate Similarity	NPC220229
0.8165	Intermediate Similarity	NPC83744
0.8165	Intermediate Similarity	NPC475060
0.8155	Intermediate Similarity	NPC196227
0.8155	Intermediate Similarity	NPC217624
0.8155	Intermediate Similarity	NPC181393
0.8137	Intermediate Similarity	NPC116726
0.8136	Intermediate Similarity	NPC473919
0.8136	Intermediate Similarity	NPC473709
0.8091	Intermediate Similarity	NPC329417
0.8077	Intermediate Similarity	NPC476245
0.8073	Intermediate Similarity	NPC214264
0.8073	Intermediate Similarity	NPC171137
0.8073	Intermediate Similarity	NPC150531
0.8073	Intermediate Similarity	NPC260268
0.8073	Intermediate Similarity	NPC48733
0.8073	Intermediate Similarity	NPC149047
0.8073	Intermediate Similarity	NPC50692
0.8073	Intermediate Similarity	NPC296945
0.8073	Intermediate Similarity	NPC257353
0.8073	Intermediate Similarity	NPC476027
0.8073	Intermediate Similarity	NPC319077
0.8073	Intermediate Similarity	NPC152695
0.8073	Intermediate Similarity	NPC202167
0.8073	Intermediate Similarity	NPC85829
0.8073	Intermediate Similarity	NPC49958
0.8073	Intermediate Similarity	NPC302607
0.8073	Intermediate Similarity	NPC97202
0.807	Intermediate Similarity	NPC179626
0.8056	Intermediate Similarity	NPC247957
0.8056	Intermediate Similarity	NPC249187
0.8051	Intermediate Similarity	NPC473802
0.8039	Intermediate Similarity	NPC473099
0.8	Intermediate Similarity	NPC471940
0.8	Intermediate Similarity	NPC117133
0.7982	Intermediate Similarity	NPC209502
0.7982	Intermediate Similarity	NPC204833
0.7981	Intermediate Similarity	NPC103527
0.7966	Intermediate Similarity	NPC222688
0.7944	Intermediate Similarity	NPC470074
0.7941	Intermediate Similarity	NPC473100
0.7934	Intermediate Similarity	NPC236999
0.792	Intermediate Similarity	NPC243902
0.7917	Intermediate Similarity	NPC471939
0.7909	Intermediate Similarity	NPC166607
0.7905	Intermediate Similarity	NPC261341
0.7895	Intermediate Similarity	NPC317210
0.789	Intermediate Similarity	NPC191892
0.7864	Intermediate Similarity	NPC134321
0.7857	Intermediate Similarity	NPC87335
0.7818	Intermediate Similarity	NPC160843
0.7807	Intermediate Similarity	NPC472002
0.7807	Intermediate Similarity	NPC207251
0.7798	Intermediate Similarity	NPC473424
0.7798	Intermediate Similarity	NPC477915
0.7788	Intermediate Similarity	NPC76084
0.7778	Intermediate Similarity	NPC154072
0.7778	Intermediate Similarity	NPC251310
0.7769	Intermediate Similarity	NPC225049
0.7769	Intermediate Similarity	NPC217901
0.7748	Intermediate Similarity	NPC323834
0.7742	Intermediate Similarity	NPC90814
0.7742	Intermediate Similarity	NPC189393
0.7736	Intermediate Similarity	NPC272617
0.7727	Intermediate Similarity	NPC311612
0.7724	Intermediate Similarity	NPC162495
0.7723	Intermediate Similarity	NPC471267
0.7719	Intermediate Similarity	NPC474229
0.7714	Intermediate Similarity	NPC125180
0.7712	Intermediate Similarity	NPC472667
0.7706	Intermediate Similarity	NPC470184
0.7705	Intermediate Similarity	NPC168849
0.7705	Intermediate Similarity	NPC475273
0.7692	Intermediate Similarity	NPC27999
0.7692	Intermediate Similarity	NPC477116
0.7692	Intermediate Similarity	NPC471854
0.7692	Intermediate Similarity	NPC128672
0.768	Intermediate Similarity	NPC476111
0.7679	Intermediate Similarity	NPC185
0.7679	Intermediate Similarity	NPC165873
0.7679	Intermediate Similarity	NPC67321
0.7679	Intermediate Similarity	NPC187435
0.7672	Intermediate Similarity	NPC326542
0.7661	Intermediate Similarity	NPC251564
0.7661	Intermediate Similarity	NPC475606
0.7661	Intermediate Similarity	NPC475314
0.7661	Intermediate Similarity	NPC477189
0.7652	Intermediate Similarity	NPC474516
0.7647	Intermediate Similarity	NPC143755
0.7642	Intermediate Similarity	NPC258674
0.7642	Intermediate Similarity	NPC472976
0.7642	Intermediate Similarity	NPC472977
0.7636	Intermediate Similarity	NPC470840
0.7636	Intermediate Similarity	NPC87351
0.7632	Intermediate Similarity	NPC235077
0.7632	Intermediate Similarity	NPC5103
0.7619	Intermediate Similarity	NPC131872
0.7615	Intermediate Similarity	NPC127408
0.7615	Intermediate Similarity	NPC291785
0.7615	Intermediate Similarity	NPC144956
0.7611	Intermediate Similarity	NPC29827
0.76	Intermediate Similarity	NPC473485
0.76	Intermediate Similarity	NPC180902
0.76	Intermediate Similarity	NPC475139
0.76	Intermediate Similarity	NPC474508
0.7593	Intermediate Similarity	NPC474785
0.7593	Intermediate Similarity	NPC18509
0.7593	Intermediate Similarity	NPC474938
0.7586	Intermediate Similarity	NPC250109
0.7586	Intermediate Similarity	NPC962
0.7586	Intermediate Similarity	NPC474271
0.7586	Intermediate Similarity	NPC49451
0.757	Intermediate Similarity	NPC473170
0.757	Intermediate Similarity	NPC271195
0.7568	Intermediate Similarity	NPC111323
0.7568	Intermediate Similarity	NPC270046
0.7568	Intermediate Similarity	NPC131366
0.7565	Intermediate Similarity	NPC171888
0.7565	Intermediate Similarity	NPC146945
0.7549	Intermediate Similarity	NPC79573
0.7547	Intermediate Similarity	NPC109305
0.7545	Intermediate Similarity	NPC237190
0.7545	Intermediate Similarity	NPC112613
0.7545	Intermediate Similarity	NPC207885
0.7544	Intermediate Similarity	NPC273433
0.7544	Intermediate Similarity	NPC141350
0.7542	Intermediate Similarity	NPC97908
0.7542	Intermediate Similarity	NPC122033
0.7542	Intermediate Similarity	NPC470775
0.7542	Intermediate Similarity	NPC176513

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 NPC163004 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	199
0.1-0.2	1947
0.2-0.3	3861
0.3-0.4	2088
0.4-0.5	668
0.5-0.6	237
0.6-0.7	141
0.7-0.8	9
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
0.7798	Intermediate Similarity	NPD5211	Phase 2
0.7658	Intermediate Similarity	NPD5141	Approved
0.7632	Intermediate Similarity	NPD4634	Approved
0.7615	Intermediate Similarity	NPD5285	Approved
0.7615	Intermediate Similarity	NPD5286	Approved
0.7615	Intermediate Similarity	NPD4696	Approved
0.7593	Intermediate Similarity	NPD4755	Approved
0.7478	Intermediate Similarity	NPD6371	Approved
0.7477	Intermediate Similarity	NPD5225	Approved
0.7477	Intermediate Similarity	NPD5224	Approved
0.7477	Intermediate Similarity	NPD5226	Approved
0.7477	Intermediate Similarity	NPD4633	Approved
0.7455	Intermediate Similarity	NPD4700	Approved
0.7411	Intermediate Similarity	NPD5174	Approved
0.7411	Intermediate Similarity	NPD5175	Approved
0.7387	Intermediate Similarity	NPD5223	Approved
0.7379	Intermediate Similarity	NPD1696	Phase 3
0.7288	Intermediate Similarity	NPD4632	Approved
0.7217	Intermediate Similarity	NPD5697	Approved
0.7182	Intermediate Similarity	NPD5220	Clinical (unspecified phase)
0.7182	Intermediate Similarity	NPD4697	Phase 3
0.7182	Intermediate Similarity	NPD5221	Approved
0.7182	Intermediate Similarity	NPD5222	Approved
0.7155	Intermediate Similarity	NPD6881	Approved
0.7155	Intermediate Similarity	NPD4729	Approved
0.7155	Intermediate Similarity	NPD6899	Approved
0.7155	Intermediate Similarity	NPD4730	Approved
0.7155	Intermediate Similarity	NPD5128	Approved
0.713	Intermediate Similarity	NPD7128	Approved
0.713	Intermediate Similarity	NPD5739	Approved
0.713	Intermediate Similarity	NPD6402	Approved
0.713	Intermediate Similarity	NPD6675	Approved
0.713	Intermediate Similarity	NPD4767	Approved
0.713	Intermediate Similarity	NPD4768	Approved
0.7119	Intermediate Similarity	NPD6650	Approved
0.7119	Intermediate Similarity	NPD6649	Approved
0.7117	Intermediate Similarity	NPD5173	Approved
0.7107	Intermediate Similarity	NPD7115	Discovery
0.7105	Intermediate Similarity	NPD4754	Approved
0.7103	Intermediate Similarity	NPD4753	Phase 2
0.7094	Intermediate Similarity	NPD6373	Approved
0.7094	Intermediate Similarity	NPD6013	Approved
0.7094	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7094	Intermediate Similarity	NPD6372	Approved
0.7094	Intermediate Similarity	NPD6012	Approved
0.7094	Intermediate Similarity	NPD6014	Approved
0.7091	Intermediate Similarity	NPD4629	Approved
0.7091	Intermediate Similarity	NPD5210	Approved
0.7073	Intermediate Similarity	NPD6319	Approved
0.7069	Intermediate Similarity	NPD5701	Approved
0.7064	Intermediate Similarity	NPD4202	Approved
0.7059	Intermediate Similarity	NPD8297	Approved
0.7034	Intermediate Similarity	NPD6883	Approved
0.7034	Intermediate Similarity	NPD5250	Approved
0.7034	Intermediate Similarity	NPD5251	Approved
0.7034	Intermediate Similarity	NPD5247	Approved
0.7034	Intermediate Similarity	NPD5248	Approved
0.7034	Intermediate Similarity	NPD7102	Approved
0.7034	Intermediate Similarity	NPD5249	Phase 3
0.7034	Intermediate Similarity	NPD7290	Approved
0.7009	Intermediate Similarity	NPD7320	Approved
0.7009	Intermediate Similarity	NPD6011	Approved
0.6981	Remote Similarity	NPD3618	Phase 1
0.6975	Remote Similarity	NPD6869	Approved
0.6975	Remote Similarity	NPD8130	Phase 1
0.6975	Remote Similarity	NPD5215	Approved
0.6975	Remote Similarity	NPD6617	Approved
0.6975	Remote Similarity	NPD5217	Approved
0.6975	Remote Similarity	NPD6847	Approved
0.6975	Remote Similarity	NPD5216	Approved
0.6972	Remote Similarity	NPD6079	Approved
0.6967	Remote Similarity	NPD6009	Approved
0.6944	Remote Similarity	NPD5328	Approved
0.6935	Remote Similarity	NPD6054	Approved
0.693	Remote Similarity	NPD5344	Discontinued
0.6917	Remote Similarity	NPD6882	Approved
0.6905	Remote Similarity	NPD7604	Phase 2
0.6903	Remote Similarity	NPD4225	Approved
0.6891	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6891	Remote Similarity	NPD5169	Approved
0.6891	Remote Similarity	NPD5134	Clinical (unspecified phase)
0.6891	Remote Similarity	NPD5135	Approved
0.688	Remote Similarity	NPD6016	Approved
0.688	Remote Similarity	NPD6015	Approved
0.6864	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6847	Remote Similarity	NPD5282	Discontinued
0.6838	Remote Similarity	NPD6008	Approved
0.6833	Remote Similarity	NPD5127	Approved
0.6825	Remote Similarity	NPD6370	Approved
0.6825	Remote Similarity	NPD5988	Approved
0.68	Remote Similarity	NPD6059	Approved
0.6748	Remote Similarity	NPD6274	Approved
0.6746	Remote Similarity	NPD5983	Phase 2
0.6719	Remote Similarity	NPD7492	Approved
0.6696	Remote Similarity	NPD7640	Approved
0.6696	Remote Similarity	NPD7639	Approved
0.6694	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD5279	Phase 3
0.6667	Remote Similarity	NPD5690	Phase 2
0.6667	Remote Similarity	NPD6616	Approved
0.6667	Remote Similarity	NPD6083	Phase 2
0.6667	Remote Similarity	NPD6084	Phase 2
0.6667	Remote Similarity	NPD5167	Approved
0.6639	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6639	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6637	Remote Similarity	NPD5695	Phase 3
0.6636	Remote Similarity	NPD4786	Approved
0.6636	Remote Similarity	NPD4197	Approved
0.6636	Remote Similarity	NPD3133	Approved
0.6636	Remote Similarity	NPD3665	Phase 1
0.6636	Remote Similarity	NPD3666	Approved
0.6615	Remote Similarity	NPD7078	Approved
0.6609	Remote Similarity	NPD7638	Approved
0.6609	Remote Similarity	NPD5696	Approved
0.6604	Remote Similarity	NPD3667	Approved
0.6587	Remote Similarity	NPD4522	Approved
0.6587	Remote Similarity	NPD7100	Approved
0.6587	Remote Similarity	NPD7101	Approved
0.6583	Remote Similarity	NPD5168	Approved
0.6574	Remote Similarity	NPD5329	Approved
0.6571	Remote Similarity	NPD4695	Discontinued
0.6565	Remote Similarity	NPD7736	Approved
0.656	Remote Similarity	NPD6317	Approved
0.6552	Remote Similarity	NPD6648	Approved
0.6538	Remote Similarity	NPD7507	Approved
0.6538	Remote Similarity	NPD6336	Discontinued
0.6518	Remote Similarity	NPD7515	Phase 2
0.6515	Remote Similarity	NPD7319	Approved
0.6514	Remote Similarity	NPD4623	Approved
0.6514	Remote Similarity	NPD4694	Approved
0.6514	Remote Similarity	NPD5280	Approved
0.6514	Remote Similarity	NPD4519	Discontinued
0.6514	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6508	Remote Similarity	NPD6335	Approved
0.6508	Remote Similarity	NPD6314	Approved
0.6508	Remote Similarity	NPD6313	Approved
0.65	Remote Similarity	NPD6412	Phase 2
0.6491	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6489	Remote Similarity	NPD8293	Discontinued
0.6484	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.646	Remote Similarity	NPD6399	Phase 3
0.6457	Remote Similarity	NPD7516	Approved
0.6455	Remote Similarity	NPD7524	Approved
0.6449	Remote Similarity	NPD4223	Phase 3
0.6449	Remote Similarity	NPD4221	Approved
0.6446	Remote Similarity	NPD6686	Approved
0.6389	Remote Similarity	NPD6110	Phase 1
0.6385	Remote Similarity	NPD8328	Phase 3
0.6379	Remote Similarity	NPD7902	Approved
0.6378	Remote Similarity	NPD7328	Approved
0.6378	Remote Similarity	NPD7327	Approved
0.6372	Remote Similarity	NPD5281	Approved
0.6372	Remote Similarity	NPD5284	Approved
0.6371	Remote Similarity	NPD6053	Discontinued
0.6357	Remote Similarity	NPD6909	Approved
0.6357	Remote Similarity	NPD6908	Approved
0.6348	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.633	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD6033	Approved
0.6316	Remote Similarity	NPD5133	Approved
0.6306	Remote Similarity	NPD4751	Clinical (unspecified phase)
0.6296	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6283	Remote Similarity	NPD5785	Approved
0.6283	Remote Similarity	NPD46	Approved
0.6283	Remote Similarity	NPD6698	Approved
0.6273	Remote Similarity	NPD5363	Approved
0.6262	Remote Similarity	NPD6930	Phase 2
0.6262	Remote Similarity	NPD6931	Approved
0.6262	Remote Similarity	NPD7525	Registered
0.6262	Remote Similarity	NPD7332	Phase 2
0.6261	Remote Similarity	NPD7748	Approved
0.6239	Remote Similarity	NPD4788	Approved
0.6239	Remote Similarity	NPD6695	Phase 3
0.6231	Remote Similarity	NPD6921	Approved
0.622	Remote Similarity	NPD6868	Approved
0.6216	Remote Similarity	NPD5205	Approved
0.6216	Remote Similarity	NPD4138	Approved
0.6216	Remote Similarity	NPD4693	Phase 3
0.6216	Remote Similarity	NPD4688	Approved
0.6216	Remote Similarity	NPD4689	Approved
0.6216	Remote Similarity	NPD4690	Approved
0.6204	Remote Similarity	NPD6902	Approved
0.6195	Remote Similarity	NPD1695	Approved
0.6182	Remote Similarity	NPD3668	Phase 3
0.6174	Remote Similarity	NPD5778	Approved
0.6174	Remote Similarity	NPD5779	Approved
0.6168	Remote Similarity	NPD6929	Approved
0.6167	Remote Similarity	NPD7632	Discontinued
0.6167	Remote Similarity	NPD5091	Approved
0.6129	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6126	Remote Similarity	NPD1694	Approved
0.6121	Remote Similarity	NPD7900	Approved
0.6121	Remote Similarity	NPD6001	Approved
0.6121	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD7514	Phase 3
0.6111	Remote Similarity	NPD8259	Clinical (unspecified phase)
0.6107	Remote Similarity	NPD8033	Approved
0.6107	Remote Similarity	NPD8335	Approved
0.6107	Remote Similarity	NPD8296	Approved
0.6107	Remote Similarity	NPD8380	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