NPASS Compound

Structure

NPC330016 OpenBabel07101719512D 25 25 0 0 1 0 0 0 0 0999 V2000 0.7459 5.7438 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2553 1.6213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5289 -2.1002 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2200 5.4850 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9965 2.5872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6594 -1.1088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4788 4.5191 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4177 1.1730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2283 3.8120 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6766 2.1390 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1248 0.4659 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 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0306 2.8461 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.0000 -2.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 1 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 0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5981 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 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 6 1 0 0 0 0 2 7 1 0 0 0 0 3 8 1 0 0 0 0 4 9 1 0 0 0 0 5 23 1 0 0 0 0 6 10 1 0 0 0 0 7 17 1 0 0 0 0 10 12 2 0 0 0 0 11 13 1 0 0 0 0 11 14 1 0 0 0 0 12 17 1 0 0 0 0 13 17 1 0 0 0 0 14 21 1 0 0 0 0 15 20 1 0 0 0 0 16 18 1 0 0 0 0 16 21 1 0 0 0 0 18 8 1 6 0 0 0 18 19 1 0 0 0 0 19 15 1 6 0 0 0 19 24 1 0 0 0 0 20 22 2 0 0 0 0 20 23 1 0 0 0 0 21 9 1 6 0 0 0 21 25 1 0 0 0 0 24 25 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	354.28
Volume:	393.104
LogP:	5.921
LogD:	4.934
LogS:	-5.656
# Rotatable Bonds:	12
TPSA:	44.76
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.275
Synthetic Accessibility Score:	4.594
Fsp3:	0.857
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.516
MDCK Permeability:	3.695455234264955e-05
Pgp-inhibitor:	0.986
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.009
30% Bioavailability (F30%):	0.665

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.188
Plasma Protein Binding (PPB):	96.12564849853516%
Volume Distribution (VD):	0.47
Pgp-substrate:	1.7319198846817017%

ADMET: Metabolism

CYP1A2-inhibitor:	0.061
CYP1A2-substrate:	0.651
CYP2C19-inhibitor:	0.217
CYP2C19-substrate:	0.924
CYP2C9-inhibitor:	0.489
CYP2C9-substrate:	0.072
CYP2D6-inhibitor:	0.372
CYP2D6-substrate:	0.486
CYP3A4-inhibitor:	0.97
CYP3A4-substrate:	0.559

ADMET: Excretion

Clearance (CL):	8.027
Half-life (T1/2):	0.257

ADMET: Toxicity

hERG Blockers:	0.222
Human Hepatotoxicity (H-HT):	0.445
Drug-inuced Liver Injury (DILI):	0.216
AMES Toxicity:	0.006
Rat Oral Acute Toxicity:	0.15
Maximum Recommended Daily Dose:	0.932
Skin Sensitization:	0.903
Carcinogencity:	0.284
Eye Corrosion:	0.136
Eye Irritation:	0.265
Respiratory Toxicity:	0.959

Download Data

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

Natural Product: NPC330016

Natural Product ID:	NPC330016
*Common Name:**	Plakortide F
IUPAC Name:	methyl 2-[(3S,4S,6S)-4,6-diethyl-6-[(E)-4-ethyloct-5-enyl]dioxan-3-yl]acetate
Synonyms:	Plakortide F
Standard InCHIKey:	JOIXERUBSWWODE-RQGNMBLMSA-N
Standard InCHI:	InChI=1S/C21H38O4/c1-6-10-12-17(7-2)13-11-14-21(9-4)16-18(8-3)19(24-25-21)15-20(22)23-5/h10,12,17-19H,6-9,11,13-16H2,1-5H3/b12-10+/t17?,18-,19-,21-/m0/s1
SMILES:	CC/C=C/C(CCC[C@]1(CC)OO[C@H]([C@H](C1)CC)CC(=O)OC)CC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL482405
PubChem CID:	10450815
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000368] Dioxanes [CHEMONTID:0001312] 1,2-dioxanes

*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
NPO22559	Plakortis halichondrioides	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11277739]
NPO32577	plakortis sp.	Species	Plakinidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[11720540]
NPO22559	Plakortis halichondrioides	Species	Plakinidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[12762801]
NPO32577	plakortis sp.	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[14738400]
NPO32577	plakortis sp.	Species	Plakinidae	Eukaryota	n.a.	rock wall at 96 m depth, near Blue Hole, Orote Peninsula, Guam	n.a.	PMID[19618913]
NPO13341	Bryopsis pennata	Species	Bryopsidaceae	Eukaryota	n.a.	Hawaiian	n.a.	PMID[19916528]
NPO32577	plakortis sp.	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20235550]
NPO22559	Plakortis halichondrioides	Species	Plakinidae	Eukaryota	n.a.	caribbean	n.a.	PMID[20738102]
NPO22559	Plakortis halichondrioides	Species	Plakinidae	Eukaryota	n.a.	Puerto Rican	n.a.	PMID[20923180]
NPO32577	plakortis sp.	Species	Plakinidae	Eukaryota	n.a.	Okinawan	n.a.	PMID[23186727]
NPO32577	plakortis sp.	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7760075]
NPO22559	Plakortis halichondrioides	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8277322]
NPO22559	Plakortis halichondrioides	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8882424]
NPO32577	plakortis sp.	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9722495]
NPO13341	Bryopsis pennata	Species	Bryopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22559	Plakortis halichondrioides	Species	Plakinidae	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	2
IC50	6
Others	6

Activity Type	# Activity
Cell Line	4
Individual Protein	4
Organism	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	IC50	=	1.25	ug.mL-1	PMID[569875]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	1.25	ug.mL-1	PMID[569875]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	2.5	ug.mL-1	PMID[569875]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	IC50	=	2.5	ug.mL-1	PMID[569875]
NPT267	Individual Protein	Neuropeptide Y receptor type 1	Homo sapiens	Activity	=	100.0	%	PMID[569877]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	Activity	=	100.0	%	PMID[569877]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	Activity	=	88.0	%	PMID[569877]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.48	ug.mL-1	PMID[569875]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.39	ug.mL-1	PMID[569875]
NPT1114	Organism	Human immunodeficiency virus	Human immunodeficiency virus	EC50	=	13000.0	nM	PMID[569875]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	EC50	>	100.0	ug.mL-1	PMID[569875]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	Inhibition	=	29.0	%	PMID[569875]
NPT2255	Organism	Toxoplasma gondii RH	Toxoplasma gondii RH	Inhibition	=	67.0	%	PMID[569875]

☑ 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 NPC330016 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	180
0.1-0.2	1246
0.2-0.3	5904
0.3-0.4	15734
0.4-0.5	8813
0.5-0.6	7924
0.6-0.7	2711
0.7-0.8	130
0.8-0.85	29
0.85-0.9	11
0.9-0.95	12
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9853	High Similarity	NPC167145
0.9437	High Similarity	NPC474447
0.9437	High Similarity	NPC469514
0.9306	High Similarity	NPC476325
0.9306	High Similarity	NPC476264
0.9167	High Similarity	NPC239127
0.9041	High Similarity	NPC281296
0.9028	High Similarity	NPC255060
0.8919	High Similarity	NPC121200
0.8904	High Similarity	NPC266119
0.8816	High Similarity	NPC476988
0.88	High Similarity	NPC82488
0.88	High Similarity	NPC308545
0.875	High Similarity	NPC238425
0.875	High Similarity	NPC474543
0.875	High Similarity	NPC472018
0.8684	High Similarity	NPC469920
0.8649	High Similarity	NPC59602
0.8649	High Similarity	NPC476987
0.8649	High Similarity	NPC152754
0.863	High Similarity	NPC474551
0.8571	High Similarity	NPC79277
0.8571	High Similarity	NPC475481
0.8571	High Similarity	NPC117960
0.8571	High Similarity	NPC172309
0.8571	High Similarity	NPC14044
0.8553	High Similarity	NPC113363
0.8472	Intermediate Similarity	NPC69462
0.8472	Intermediate Similarity	NPC472017
0.84	Intermediate Similarity	NPC475744
0.84	Intermediate Similarity	NPC474316
0.84	Intermediate Similarity	NPC476985
0.8333	Intermediate Similarity	NPC107130
0.8312	Intermediate Similarity	NPC268502
0.8312	Intermediate Similarity	NPC254996
0.8289	Intermediate Similarity	NPC122847
0.8272	Intermediate Similarity	NPC476982
0.8272	Intermediate Similarity	NPC476104
0.8267	Intermediate Similarity	NPC199445
0.8267	Intermediate Similarity	NPC60718
0.8235	Intermediate Similarity	NPC472021
0.8148	Intermediate Similarity	NPC471344
0.8125	Intermediate Similarity	NPC476983
0.8125	Intermediate Similarity	NPC69469
0.8088	Intermediate Similarity	NPC226602
0.8088	Intermediate Similarity	NPC472019
0.8088	Intermediate Similarity	NPC472020
0.8052	Intermediate Similarity	NPC145898
0.8049	Intermediate Similarity	NPC262085
0.7976	Intermediate Similarity	NPC471342
0.7976	Intermediate Similarity	NPC469866
0.7975	Intermediate Similarity	NPC274522
0.7975	Intermediate Similarity	NPC476265
0.7949	Intermediate Similarity	NPC476986
0.7949	Intermediate Similarity	NPC470905
0.7901	Intermediate Similarity	NPC475989
0.7867	Intermediate Similarity	NPC126061
0.7831	Intermediate Similarity	NPC477994
0.7831	Intermediate Similarity	NPC477993
0.7821	Intermediate Similarity	NPC469867
0.7805	Intermediate Similarity	NPC120158
0.7805	Intermediate Similarity	NPC475193
0.7805	Intermediate Similarity	NPC471343
0.7792	Intermediate Similarity	NPC475861
0.7778	Intermediate Similarity	NPC476984
0.7778	Intermediate Similarity	NPC215987
0.7778	Intermediate Similarity	NPC475395
0.7778	Intermediate Similarity	NPC306805
0.775	Intermediate Similarity	NPC103634
0.7746	Intermediate Similarity	NPC474552
0.7733	Intermediate Similarity	NPC475310
0.7722	Intermediate Similarity	NPC11796
0.7722	Intermediate Similarity	NPC218817
0.7683	Intermediate Similarity	NPC476100
0.7619	Intermediate Similarity	NPC475753
0.76	Intermediate Similarity	NPC199557
0.7595	Intermediate Similarity	NPC240170
0.7595	Intermediate Similarity	NPC120776
0.7561	Intermediate Similarity	NPC476292
0.7561	Intermediate Similarity	NPC474605
0.7558	Intermediate Similarity	NPC97577
0.7532	Intermediate Similarity	NPC470237
0.7529	Intermediate Similarity	NPC471739
0.7529	Intermediate Similarity	NPC86005
0.75	Intermediate Similarity	NPC54925
0.75	Intermediate Similarity	NPC474369
0.75	Intermediate Similarity	NPC127526
0.7439	Intermediate Similarity	NPC141810
0.7432	Intermediate Similarity	NPC284447
0.7412	Intermediate Similarity	NPC475181
0.7412	Intermediate Similarity	NPC70555
0.7412	Intermediate Similarity	NPC104961
0.7412	Intermediate Similarity	NPC70422
0.7407	Intermediate Similarity	NPC617
0.7407	Intermediate Similarity	NPC263574
0.7407	Intermediate Similarity	NPC469747
0.7407	Intermediate Similarity	NPC471740
0.7407	Intermediate Similarity	NPC28319
0.7386	Intermediate Similarity	NPC36491
0.7381	Intermediate Similarity	NPC9868
0.7375	Intermediate Similarity	NPC107668
0.7375	Intermediate Similarity	NPC474760
0.7368	Intermediate Similarity	NPC477448
0.7368	Intermediate Similarity	NPC477449
0.7363	Intermediate Similarity	NPC40812
0.7356	Intermediate Similarity	NPC118193
0.7356	Intermediate Similarity	NPC256902
0.7349	Intermediate Similarity	NPC85772
0.7349	Intermediate Similarity	NPC475936
0.7342	Intermediate Similarity	NPC324762
0.7324	Intermediate Similarity	NPC475821
0.7297	Intermediate Similarity	NPC469926
0.7294	Intermediate Similarity	NPC261380
0.7284	Intermediate Similarity	NPC474341
0.7284	Intermediate Similarity	NPC321514
0.7283	Intermediate Similarity	NPC255592
0.7283	Intermediate Similarity	NPC83895
0.7283	Intermediate Similarity	NPC308567
0.7283	Intermediate Similarity	NPC261377
0.7283	Intermediate Similarity	NPC187761
0.7273	Intermediate Similarity	NPC472955
0.7262	Intermediate Similarity	NPC53867
0.7262	Intermediate Similarity	NPC475622
0.7262	Intermediate Similarity	NPC475947
0.7262	Intermediate Similarity	NPC108045
0.725	Intermediate Similarity	NPC474527
0.725	Intermediate Similarity	NPC471726
0.725	Intermediate Similarity	NPC279537
0.7246	Intermediate Similarity	NPC128061
0.7246	Intermediate Similarity	NPC10316
0.7246	Intermediate Similarity	NPC200845
0.7246	Intermediate Similarity	NPC223677
0.7246	Intermediate Similarity	NPC28779
0.7237	Intermediate Similarity	NPC273508
0.7237	Intermediate Similarity	NPC209327
0.7229	Intermediate Similarity	NPC39411
0.7229	Intermediate Similarity	NPC281949
0.7229	Intermediate Similarity	NPC301477
0.7229	Intermediate Similarity	NPC327002
0.7229	Intermediate Similarity	NPC25684
0.7229	Intermediate Similarity	NPC88735
0.7229	Intermediate Similarity	NPC286229
0.7229	Intermediate Similarity	NPC47031
0.7229	Intermediate Similarity	NPC255580
0.7215	Intermediate Similarity	NPC166797
0.7209	Intermediate Similarity	NPC116575
0.7209	Intermediate Similarity	NPC469483
0.7206	Intermediate Similarity	NPC139545
0.7206	Intermediate Similarity	NPC309606
0.7206	Intermediate Similarity	NPC39633
0.7195	Intermediate Similarity	NPC622
0.7195	Intermediate Similarity	NPC158565
0.7195	Intermediate Similarity	NPC276647
0.7179	Intermediate Similarity	NPC320119
0.7179	Intermediate Similarity	NPC474590
0.7176	Intermediate Similarity	NPC72464
0.7176	Intermediate Similarity	NPC295799
0.7162	Intermediate Similarity	NPC234767
0.716	Intermediate Similarity	NPC470240
0.716	Intermediate Similarity	NPC476794
0.716	Intermediate Similarity	NPC97516
0.7159	Intermediate Similarity	NPC475971
0.7143	Intermediate Similarity	NPC474252
0.7143	Intermediate Similarity	NPC35556
0.7143	Intermediate Similarity	NPC475690
0.7143	Intermediate Similarity	NPC7414
0.7143	Intermediate Similarity	NPC329656
0.7143	Intermediate Similarity	NPC296522
0.7143	Intermediate Similarity	NPC144511
0.7126	Intermediate Similarity	NPC478145
0.7126	Intermediate Similarity	NPC477959
0.7126	Intermediate Similarity	NPC478144
0.7125	Intermediate Similarity	NPC244166
0.7123	Intermediate Similarity	NPC174560
0.7123	Intermediate Similarity	NPC201939
0.7123	Intermediate Similarity	NPC125312
0.7111	Intermediate Similarity	NPC478036
0.7111	Intermediate Similarity	NPC478037
0.7108	Intermediate Similarity	NPC233377
0.7105	Intermediate Similarity	NPC104537
0.7105	Intermediate Similarity	NPC475443
0.7105	Intermediate Similarity	NPC127091
0.7105	Intermediate Similarity	NPC271921
0.7105	Intermediate Similarity	NPC473829
0.7105	Intermediate Similarity	NPC330426
0.7105	Intermediate Similarity	NPC22101
0.7105	Intermediate Similarity	NPC148192
0.7093	Intermediate Similarity	NPC125290
0.7093	Intermediate Similarity	NPC76333
0.7089	Intermediate Similarity	NPC135703
0.7079	Intermediate Similarity	NPC473448
0.7079	Intermediate Similarity	NPC253144
0.7079	Intermediate Similarity	NPC51653
0.7073	Intermediate Similarity	NPC192006
0.7067	Intermediate Similarity	NPC326268
0.7067	Intermediate Similarity	NPC476330
0.7067	Intermediate Similarity	NPC318420
0.7065	Intermediate Similarity	NPC469528
0.7065	Intermediate Similarity	NPC469369
0.7059	Intermediate Similarity	NPC11620

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 NPC330016 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	157
0.1-0.2	1761
0.2-0.3	4023
0.3-0.4	2156
0.4-0.5	608
0.5-0.6	363
0.6-0.7	77
0.7-0.8	5
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
0.7654	Intermediate Similarity	NPD5369	Approved
0.7558	Intermediate Similarity	NPD5764	Clinical (unspecified phase)
0.7558	Intermediate Similarity	NPD6101	Approved
0.7386	Intermediate Similarity	NPD6411	Approved
0.7349	Intermediate Similarity	NPD6435	Approved
0.7317	Intermediate Similarity	NPD5368	Approved
0.7143	Intermediate Similarity	NPD4270	Approved
0.7143	Intermediate Similarity	NPD4269	Approved
0.7111	Intermediate Similarity	NPD5779	Approved
0.7111	Intermediate Similarity	NPD5778	Approved
0.7108	Intermediate Similarity	NPD4820	Approved
0.7108	Intermediate Similarity	NPD4819	Approved
0.7108	Intermediate Similarity	NPD4822	Approved
0.7108	Intermediate Similarity	NPD4821	Approved
0.7059	Intermediate Similarity	NPD7154	Phase 3
0.7011	Intermediate Similarity	NPD5786	Approved
0.7	Intermediate Similarity	NPD7983	Approved
0.6914	Remote Similarity	NPD8039	Approved
0.6912	Remote Similarity	NPD28	Approved
0.6912	Remote Similarity	NPD29	Approved
0.6905	Remote Similarity	NPD4252	Approved
0.6905	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD5363	Approved
0.6889	Remote Similarity	NPD46	Approved
0.6889	Remote Similarity	NPD6698	Approved
0.6882	Remote Similarity	NPD7839	Suspended
0.6867	Remote Similarity	NPD4268	Approved
0.6867	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6867	Remote Similarity	NPD4271	Approved
0.686	Remote Similarity	NPD5362	Discontinued
0.6848	Remote Similarity	NPD5282	Discontinued
0.6711	Remote Similarity	NPD3197	Phase 1
0.6703	Remote Similarity	NPD5785	Approved
0.6667	Remote Similarity	NPD3732	Approved
0.6629	Remote Similarity	NPD7521	Approved
0.6629	Remote Similarity	NPD7146	Approved
0.6629	Remote Similarity	NPD6422	Discontinued
0.6629	Remote Similarity	NPD6409	Approved
0.6629	Remote Similarity	NPD7334	Approved
0.6629	Remote Similarity	NPD6684	Approved
0.6629	Remote Similarity	NPD5330	Approved
0.662	Remote Similarity	NPD3196	Approved
0.662	Remote Similarity	NPD3194	Approved
0.662	Remote Similarity	NPD3195	Phase 2
0.662	Remote Similarity	NPD4266	Approved
0.6596	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6559	Remote Similarity	NPD6399	Phase 3
0.6552	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6538	Remote Similarity	NPD7331	Phase 2
0.6489	Remote Similarity	NPD7900	Approved
0.6489	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD6903	Approved
0.6484	Remote Similarity	NPD5737	Approved
0.6484	Remote Similarity	NPD6672	Approved
0.6479	Remote Similarity	NPD3172	Approved
0.6452	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.6413	Remote Similarity	NPD1695	Approved
0.6413	Remote Similarity	NPD5370	Suspended
0.641	Remote Similarity	NPD7341	Phase 2
0.641	Remote Similarity	NPD2685	Clinical (unspecified phase)
0.6374	Remote Similarity	NPD4250	Approved
0.6374	Remote Similarity	NPD3573	Approved
0.6374	Remote Similarity	NPD4251	Approved
0.6364	Remote Similarity	NPD5209	Approved
0.6354	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.6333	Remote Similarity	NPD1694	Approved
0.6333	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD7748	Approved
0.6292	Remote Similarity	NPD5332	Approved
0.6292	Remote Similarity	NPD5331	Approved
0.6289	Remote Similarity	NPD6084	Phase 2
0.6289	Remote Similarity	NPD7902	Approved
0.6289	Remote Similarity	NPD6083	Phase 2
0.6277	Remote Similarity	NPD7637	Suspended
0.6277	Remote Similarity	NPD7515	Phase 2
0.6275	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6264	Remote Similarity	NPD6098	Approved
0.6264	Remote Similarity	NPD4249	Approved
0.625	Remote Similarity	NPD5695	Phase 3
0.625	Remote Similarity	NPD4790	Discontinued
0.6237	Remote Similarity	NPD6904	Approved
0.6237	Remote Similarity	NPD6673	Approved
0.6237	Remote Similarity	NPD6080	Approved
0.6232	Remote Similarity	NPD5343	Approved
0.6214	Remote Similarity	NPD6881	Approved
0.6214	Remote Similarity	NPD6899	Approved
0.619	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6176	Remote Similarity	NPD6402	Approved
0.6176	Remote Similarity	NPD3174	Discontinued
0.6176	Remote Similarity	NPD7128	Approved
0.6176	Remote Similarity	NPD5739	Approved
0.6176	Remote Similarity	NPD6675	Approved
0.617	Remote Similarity	NPD7838	Discovery
0.6154	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6125	Remote Similarity	NPD6108	Clinical (unspecified phase)
0.6117	Remote Similarity	NPD5697	Approved
0.6105	Remote Similarity	NPD5694	Approved
0.6105	Remote Similarity	NPD5284	Approved
0.6105	Remote Similarity	NPD6050	Approved
0.6105	Remote Similarity	NPD5281	Approved
0.6104	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.6095	Remote Similarity	NPD7290	Approved
0.6095	Remote Similarity	NPD7102	Approved
0.6095	Remote Similarity	NPD6883	Approved
0.6095	Remote Similarity	NPD6371	Approved
0.6082	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6061	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6061	Remote Similarity	NPD5696	Approved
0.6058	Remote Similarity	NPD6686	Approved
0.6058	Remote Similarity	NPD7320	Approved
0.6058	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6044	Remote Similarity	NPD4786	Approved
0.6044	Remote Similarity	NPD3668	Phase 3
0.6038	Remote Similarity	NPD6847	Approved
0.6038	Remote Similarity	NPD8130	Phase 1
0.6038	Remote Similarity	NPD6650	Approved
0.6038	Remote Similarity	NPD6617	Approved
0.6038	Remote Similarity	NPD6869	Approved
0.6038	Remote Similarity	NPD6649	Approved
0.6	Remote Similarity	NPD6014	Approved
0.6	Remote Similarity	NPD5692	Phase 3
0.6	Remote Similarity	NPD6372	Approved
0.6	Remote Similarity	NPD6013	Approved
0.6	Remote Similarity	NPD3667	Approved
0.6	Remote Similarity	NPD5207	Approved
0.6	Remote Similarity	NPD6012	Approved
0.6	Remote Similarity	NPD6373	Approved
0.5981	Remote Similarity	NPD6882	Approved
0.5981	Remote Similarity	NPD8297	Approved
0.5962	Remote Similarity	NPD5701	Approved
0.5957	Remote Similarity	NPD5208	Approved
0.5946	Remote Similarity	NPD3729	Clinical (unspecified phase)
0.5938	Remote Similarity	NPD8034	Phase 2
0.5938	Remote Similarity	NPD5693	Phase 1
0.5938	Remote Similarity	NPD8035	Phase 2
0.5915	Remote Similarity	NPD3173	Approved
0.5909	Remote Similarity	NPD4238	Approved
0.5909	Remote Similarity	NPD4802	Phase 2
0.5909	Remote Similarity	NPD7115	Discovery
0.5905	Remote Similarity	NPD6011	Approved
0.59	Remote Similarity	NPD4225	Approved
0.5895	Remote Similarity	NPD4753	Phase 2
0.5895	Remote Similarity	NPD6051	Approved
0.5876	Remote Similarity	NPD5781	Clinical (unspecified phase)
0.5875	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.5875	Remote Similarity	NPD7909	Approved
0.587	Remote Similarity	NPD3665	Phase 1
0.587	Remote Similarity	NPD3133	Approved
0.587	Remote Similarity	NPD3666	Approved
0.5865	Remote Similarity	NPD6008	Approved
0.5854	Remote Similarity	NPD4247	Clinical (unspecified phase)
0.5842	Remote Similarity	NPD5286	Approved
0.5842	Remote Similarity	NPD6648	Approved
0.5842	Remote Similarity	NPD4696	Approved
0.5842	Remote Similarity	NPD7798	Approved
0.5842	Remote Similarity	NPD5285	Approved
0.5841	Remote Similarity	NPD8513	Phase 3
0.5841	Remote Similarity	NPD8517	Approved
0.5841	Remote Similarity	NPD8515	Approved
0.5841	Remote Similarity	NPD8516	Approved
0.5833	Remote Similarity	NPD3672	Approved
0.5833	Remote Similarity	NPD3673	Approved
0.5833	Remote Similarity	NPD6053	Discontinued
0.5826	Remote Similarity	NPD8342	Approved
0.5826	Remote Similarity	NPD8340	Approved
0.5826	Remote Similarity	NPD8341	Approved
0.5826	Remote Similarity	NPD8299	Approved
0.581	Remote Similarity	NPD6685	Approved
0.581	Remote Similarity	NPD6412	Phase 2
0.5806	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.5802	Remote Similarity	NPD9496	Clinical (unspecified phase)
0.58	Remote Similarity	NPD4755	Approved
0.5797	Remote Similarity	NPD6097	Approved
0.5797	Remote Similarity	NPD2699	Approved
0.5797	Remote Similarity	NPD6096	Approved
0.5795	Remote Similarity	NPD4756	Discovery
0.5784	Remote Similarity	NPD5344	Discontinued
0.5783	Remote Similarity	NPD229	Approved
0.5778	Remote Similarity	NPD4695	Discontinued
0.5778	Remote Similarity	NPD8259	Clinical (unspecified phase)
0.5776	Remote Similarity	NPD8273	Phase 1
0.5776	Remote Similarity	NPD8451	Approved
0.5775	Remote Similarity	NPD622	Approved
0.5775	Remote Similarity	NPD6125	Clinical (unspecified phase)
0.5773	Remote Similarity	NPD6079	Approved
0.5769	Remote Similarity	NPD3198	Approved
0.5758	Remote Similarity	NPD4629	Approved
0.5758	Remote Similarity	NPD5210	Approved
0.5752	Remote Similarity	NPD6319	Approved
0.5745	Remote Similarity	NPD3618	Phase 1
0.5745	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.5745	Remote Similarity	NPD5279	Phase 3
0.5743	Remote Similarity	NPD7638	Approved
0.5741	Remote Similarity	NPD1719	Phase 1
0.5741	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.5729	Remote Similarity	NPD5328	Approved
0.5729	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.5728	Remote Similarity	NPD5226	Approved
0.5728	Remote Similarity	NPD5224	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