NPASS Compound

Structure

CID14141 OpenBabel06191715342D 26 28 0 0 1 0 0 0 0 0999 V2000 -2.2398 1.1499 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9122 -1.7466 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0760 -0.2984 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2428 -2.6812 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3477 -3.1980 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7483 -1.2639 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9122 0.1844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5411 -3.5995 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0493 -4.1163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2398 -1.7466 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0760 -1.2639 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2984 -2.4805 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7483 -0.2984 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8951 -4.3170 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.5622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9183 -1.2639 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9183 -0.2984 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4037 -0.2984 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5675 -0.7811 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5845 0.1844 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1934 -5.2353 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6994 -1.8314 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6994 0.2692 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2398 -0.7811 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4037 0.6672 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 25 1 0 0 0 0 2 6 1 0 0 0 0 2 11 2 0 0 0 0 3 7 2 0 0 0 0 3 11 1 0 0 0 0 4 8 1 0 0 0 0 4 12 2 0 0 0 0 5 9 2 0 0 0 0 5 12 1 0 0 0 0 6 13 2 0 0 0 0 7 13 1 0 0 0 0 8 14 2 0 0 0 0 9 14 1 0 0 0 0 10 11 1 0 0 0 0 12 15 1 0 0 0 0 13 20 1 0 0 0 0 14 21 1 0 0 0 0 15 16 2 0 0 0 0 15 19 1 0 0 0 0 16 17 1 0 0 0 0 16 22 1 0 0 0 0 17 23 2 0 0 0 0 17 26 1 0 0 0 0 18 19 1 0 0 0 0 18 24 2 0 0 0 0 18 25 1 0 0 0 0 19 10 1 1 0 0 0 19 26 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	356.09
Volume:	349.314
LogP:	2.226
LogD:	1.96
LogS:	-3.631
# Rotatable Bonds:	5
TPSA:	110.13
# H-Bond Aceptor:	7
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.63
Synthetic Accessibility Score:	3.464
Fsp3:	0.211
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:	-4.91
MDCK Permeability:	1.7443318938603625e-05
Pgp-inhibitor:	0.01
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.3
30% Bioavailability (F30%):	0.941

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.043
Plasma Protein Binding (PPB):	94.86835479736328%
Volume Distribution (VD):	0.296
Pgp-substrate:	7.360472679138184%

ADMET: Metabolism

CYP1A2-inhibitor:	0.153
CYP1A2-substrate:	0.578
CYP2C19-inhibitor:	0.943
CYP2C19-substrate:	0.098
CYP2C9-inhibitor:	0.907
CYP2C9-substrate:	0.914
CYP2D6-inhibitor:	0.542
CYP2D6-substrate:	0.678
CYP3A4-inhibitor:	0.844
CYP3A4-substrate:	0.363

ADMET: Excretion

Clearance (CL):	12.854
Half-life (T1/2):	0.686

ADMET: Toxicity

hERG Blockers:	0.041
Human Hepatotoxicity (H-HT):	0.189
Drug-inuced Liver Injury (DILI):	0.682
AMES Toxicity:	0.191
Rat Oral Acute Toxicity:	0.25
Maximum Recommended Daily Dose:	0.033
Skin Sensitization:	0.142
Carcinogencity:	0.336
Eye Corrosion:	0.003
Eye Irritation:	0.074
Respiratory Toxicity:	0.024

Download Data

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

Natural Product: NPC14141

Natural Product ID:	NPC14141
*Common Name:**	Butyrolactone Ii
IUPAC Name:	methyl (2R)-4-hydroxy-3-(4-hydroxyphenyl)-2-[(4-hydroxyphenyl)methyl]-5-oxofuran-2-carboxylate
Synonyms:
Standard InCHIKey:	AEKPZNDJHWFONI-LJQANCHMSA-N
Standard InCHI:	InChI=1S/C19H16O7/c1-25-18(24)19(10-11-2-6-13(20)7-3-11)15(16(22)17(23)26-19)12-4-8-14(21)9-5-12/h2-9,20-22H,10H2,1H3/t19-/m1/s1
SMILES:	COC(=O)[C@@]1(Cc2ccc(cc2)O)C(=C(C(=O)O1)O)c1ccc(cc1)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL3753562
PubChem CID:	10405953
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000324] Fatty acid esters

*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
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21049973]
NPO41081	Aspergillus sp. CPCC 400735	Strain	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29016131]
NPO12352	Magnolia baillonii	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3437284]
NPO19551	Cocculus pendulus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19551	Cocculus pendulus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16902	Dendroctonus brevicomis	Species	Curculionidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11741	Glycosmis parviflora	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18651	Piper lolot	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18223	Dictyostelium brefeldianum	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19146	Cosmos bipinnatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19551	Cocculus pendulus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14131	Phyllanthus maderaspatensis	Species	Phyllanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19681	Hypoxis filiformis	Species	Hypoxidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18898	Madhuca utilis	Species	Sapotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17984	Aplysia angasi	Species	Aplysiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10921	Cercospora ligustri	Species	Mycosphaerellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12352	Magnolia baillonii	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19611	Ipomoea tuberosa	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13189	Carex folliculata	Species	Cyperaceae	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
IC50	4
Others	2

Activity Type	# Activity
Cell Line	1
Organism	2
Others	2
PROTEIN FAMILY	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2157	Cell Line	SUP-T1	Homo sapiens	CC50	>	100000.0	nM	PMID[528494]
NPT2	Others	Unspecified		IC50	=	126.0	nM	PMID[528493]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	IC50	=	84500.0	nM	PMID[528494]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	Inhibition	=	60.8	%	PMID[528494]
NPT20648	PROTEIN FAMILY	Alpha glucosidase	Homo sapiens	IC50	=	85130.0	nM	PMID[528495]
NPT35	Others	n.a.		IC50	=	86000.0	nM	PMID[528495]

☑ 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 NPC14141 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	261
0.1-0.2	1185
0.2-0.3	3012
0.3-0.4	7641
0.4-0.5	11213
0.5-0.6	5580
0.6-0.7	11777
0.7-0.8	1924
0.8-0.85	79
0.85-0.9	14
0.9-0.95	9
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9587	High Similarity	NPC217431
0.9206	High Similarity	NPC202743
0.9153	High Similarity	NPC471033
0.9153	High Similarity	NPC311091
0.9127	High Similarity	NPC173034
0.8983	High Similarity	NPC128249
0.8898	High Similarity	NPC108553
0.8644	High Similarity	NPC48525
0.8644	High Similarity	NPC17693
0.864	High Similarity	NPC288945
0.8615	High Similarity	NPC155209
0.8615	High Similarity	NPC168799
0.8605	High Similarity	NPC198388
0.856	High Similarity	NPC473942
0.8547	High Similarity	NPC79543
0.8538	High Similarity	NPC18074
0.8538	High Similarity	NPC25581
0.8538	High Similarity	NPC61
0.8538	High Similarity	NPC5419
0.8496	Intermediate Similarity	NPC279676
0.8496	Intermediate Similarity	NPC67349
0.8475	Intermediate Similarity	NPC183700
0.8473	Intermediate Similarity	NPC477281
0.8473	Intermediate Similarity	NPC477280
0.8473	Intermediate Similarity	NPC19719
0.843	Intermediate Similarity	NPC296526
0.8397	Intermediate Similarity	NPC327204
0.8397	Intermediate Similarity	NPC323379
0.837	Intermediate Similarity	NPC179505
0.837	Intermediate Similarity	NPC156709
0.8333	Intermediate Similarity	NPC469927
0.8305	Intermediate Similarity	NPC281604
0.8305	Intermediate Similarity	NPC31274
0.8296	Intermediate Similarity	NPC284409
0.8291	Intermediate Similarity	NPC70843
0.8284	Intermediate Similarity	NPC90431
0.8281	Intermediate Similarity	NPC137416
0.8279	Intermediate Similarity	NPC23402
0.8268	Intermediate Similarity	NPC236981
0.8261	Intermediate Similarity	NPC122491
0.8261	Intermediate Similarity	NPC32
0.8261	Intermediate Similarity	NPC304956
0.8235	Intermediate Similarity	NPC326187
0.8235	Intermediate Similarity	NPC289690
0.8235	Intermediate Similarity	NPC88141
0.8235	Intermediate Similarity	NPC288452
0.822	Intermediate Similarity	NPC260952
0.822	Intermediate Similarity	NPC156648
0.8211	Intermediate Similarity	NPC19290
0.8211	Intermediate Similarity	NPC28951
0.8211	Intermediate Similarity	NPC325646
0.8209	Intermediate Similarity	NPC70680
0.8209	Intermediate Similarity	NPC233350
0.8209	Intermediate Similarity	NPC182217
0.8201	Intermediate Similarity	NPC258671
0.8201	Intermediate Similarity	NPC53884
0.8175	Intermediate Similarity	NPC470848
0.8175	Intermediate Similarity	NPC470849
0.8169	Intermediate Similarity	NPC32197
0.8167	Intermediate Similarity	NPC63345
0.8167	Intermediate Similarity	NPC21162
0.8162	Intermediate Similarity	NPC283560
0.8162	Intermediate Similarity	NPC24295
0.816	Intermediate Similarity	NPC263386
0.816	Intermediate Similarity	NPC141791
0.816	Intermediate Similarity	NPC264976
0.8151	Intermediate Similarity	NPC206341
0.8145	Intermediate Similarity	NPC76308
0.8145	Intermediate Similarity	NPC325295
0.8136	Intermediate Similarity	NPC69332
0.8136	Intermediate Similarity	NPC188677
0.8136	Intermediate Similarity	NPC29989
0.8136	Intermediate Similarity	NPC95178
0.8134	Intermediate Similarity	NPC300776
0.8134	Intermediate Similarity	NPC68779
0.8134	Intermediate Similarity	NPC68517
0.8134	Intermediate Similarity	NPC5310
0.8134	Intermediate Similarity	NPC176814
0.8134	Intermediate Similarity	NPC4982
0.813	Intermediate Similarity	NPC51345
0.812	Intermediate Similarity	NPC120693
0.812	Intermediate Similarity	NPC302844
0.812	Intermediate Similarity	NPC261573
0.812	Intermediate Similarity	NPC8931
0.8116	Intermediate Similarity	NPC253722
0.8116	Intermediate Similarity	NPC253481
0.8116	Intermediate Similarity	NPC31751
0.811	Intermediate Similarity	NPC472271
0.8106	Intermediate Similarity	NPC172673
0.8102	Intermediate Similarity	NPC59775
0.8102	Intermediate Similarity	NPC256162
0.8099	Intermediate Similarity	NPC470355
0.8092	Intermediate Similarity	NPC2596
0.8092	Intermediate Similarity	NPC79332
0.8085	Intermediate Similarity	NPC283081
0.8085	Intermediate Similarity	NPC299090
0.8085	Intermediate Similarity	NPC143892
0.8085	Intermediate Similarity	NPC221383
0.8077	Intermediate Similarity	NPC303680
0.8077	Intermediate Similarity	NPC90128
0.8077	Intermediate Similarity	NPC84076
0.8074	Intermediate Similarity	NPC311742
0.8062	Intermediate Similarity	NPC89630
0.8051	Intermediate Similarity	NPC127676
0.8051	Intermediate Similarity	NPC13495
0.8049	Intermediate Similarity	NPC285350
0.8049	Intermediate Similarity	NPC221870
0.8047	Intermediate Similarity	NPC139171
0.8045	Intermediate Similarity	NPC318799
0.8043	Intermediate Similarity	NPC38473
0.8043	Intermediate Similarity	NPC477279
0.803	Intermediate Similarity	NPC214246
0.803	Intermediate Similarity	NPC477300
0.803	Intermediate Similarity	NPC241354
0.803	Intermediate Similarity	NPC304622
0.8015	Intermediate Similarity	NPC64230
0.8015	Intermediate Similarity	NPC276466
0.8015	Intermediate Similarity	NPC71638
0.8015	Intermediate Similarity	NPC255428
0.8015	Intermediate Similarity	NPC123722
0.8015	Intermediate Similarity	NPC151167
0.8015	Intermediate Similarity	NPC123228
0.8015	Intermediate Similarity	NPC5018
0.8	Intermediate Similarity	NPC106406
0.8	Intermediate Similarity	NPC610
0.8	Intermediate Similarity	NPC248150
0.8	Intermediate Similarity	NPC175799
0.8	Intermediate Similarity	NPC474692
0.8	Intermediate Similarity	NPC88403
0.8	Intermediate Similarity	NPC257589
0.8	Intermediate Similarity	NPC145023
0.8	Intermediate Similarity	NPC53305
0.8	Intermediate Similarity	NPC200988
0.8	Intermediate Similarity	NPC280767
0.7986	Intermediate Similarity	NPC477278
0.7986	Intermediate Similarity	NPC477277
0.7985	Intermediate Similarity	NPC239302
0.7971	Intermediate Similarity	NPC26241
0.7971	Intermediate Similarity	NPC205751
0.7971	Intermediate Similarity	NPC295492
0.7971	Intermediate Similarity	NPC274891
0.7971	Intermediate Similarity	NPC476819
0.7971	Intermediate Similarity	NPC303683
0.7971	Intermediate Similarity	NPC476820
0.7971	Intermediate Similarity	NPC474875
0.797	Intermediate Similarity	NPC30390
0.797	Intermediate Similarity	NPC237506
0.797	Intermediate Similarity	NPC217052
0.797	Intermediate Similarity	NPC32626
0.797	Intermediate Similarity	NPC329344
0.7969	Intermediate Similarity	NPC147654
0.7967	Intermediate Similarity	NPC148969
0.7958	Intermediate Similarity	NPC229264
0.7955	Intermediate Similarity	NPC226661
0.7955	Intermediate Similarity	NPC110313
0.7951	Intermediate Similarity	NPC139946
0.7951	Intermediate Similarity	NPC177576
0.7945	Intermediate Similarity	NPC477299
0.7939	Intermediate Similarity	NPC204579
0.7939	Intermediate Similarity	NPC179777
0.7939	Intermediate Similarity	NPC474476
0.7939	Intermediate Similarity	NPC92207
0.7939	Intermediate Similarity	NPC127937
0.7939	Intermediate Similarity	NPC110211
0.7939	Intermediate Similarity	NPC213552
0.7939	Intermediate Similarity	NPC120225
0.7937	Intermediate Similarity	NPC104514
0.7937	Intermediate Similarity	NPC275519
0.7937	Intermediate Similarity	NPC309434
0.7937	Intermediate Similarity	NPC203124
0.7937	Intermediate Similarity	NPC293424
0.7937	Intermediate Similarity	NPC86198
0.7934	Intermediate Similarity	NPC471954
0.7934	Intermediate Similarity	NPC75272
0.7931	Intermediate Similarity	NPC245561
0.7929	Intermediate Similarity	NPC472016
0.7929	Intermediate Similarity	NPC220664
0.7929	Intermediate Similarity	NPC192831
0.7929	Intermediate Similarity	NPC258469
0.7929	Intermediate Similarity	NPC303090
0.7929	Intermediate Similarity	NPC277315
0.7929	Intermediate Similarity	NPC319628
0.7929	Intermediate Similarity	NPC284948
0.7929	Intermediate Similarity	NPC37331
0.7929	Intermediate Similarity	NPC43158
0.7923	Intermediate Similarity	NPC85565
0.792	Intermediate Similarity	NPC277394
0.792	Intermediate Similarity	NPC299252
0.792	Intermediate Similarity	NPC61062
0.7914	Intermediate Similarity	NPC9218
0.7907	Intermediate Similarity	NPC327070
0.7902	Intermediate Similarity	NPC471076
0.7902	Intermediate Similarity	NPC192568
0.7899	Intermediate Similarity	NPC86087
0.7899	Intermediate Similarity	NPC37250
0.7899	Intermediate Similarity	NPC152942
0.7899	Intermediate Similarity	NPC219428
0.7899	Intermediate Similarity	NPC302857
0.7899	Intermediate Similarity	NPC142703
0.7899	Intermediate Similarity	NPC278068

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 NPC14141 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	228
0.1-0.2	784
0.2-0.3	1332
0.3-0.4	2453
0.4-0.5	2262
0.5-0.6	1381
0.6-0.7	612
0.7-0.8	93
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8385	Intermediate Similarity	NPD6798	Discontinued
0.8333	Intermediate Similarity	NPD6355	Discontinued
0.8197	Intermediate Similarity	NPD690	Clinical (unspecified phase)
0.8182	Intermediate Similarity	NPD4062	Phase 3
0.8182	Intermediate Similarity	NPD6233	Phase 2
0.803	Intermediate Similarity	NPD7095	Approved
0.797	Intermediate Similarity	NPD3764	Approved
0.7934	Intermediate Similarity	NPD2067	Discontinued
0.7929	Intermediate Similarity	NPD6190	Approved
0.7852	Intermediate Similarity	NPD4060	Phase 1
0.7801	Intermediate Similarity	NPD2354	Approved
0.7795	Intermediate Similarity	NPD9545	Approved
0.7752	Intermediate Similarity	NPD3847	Discontinued
0.773	Intermediate Similarity	NPD4628	Phase 3
0.7727	Intermediate Similarity	NPD2797	Approved
0.7714	Intermediate Similarity	NPD5958	Discontinued
0.7714	Intermediate Similarity	NPD4534	Discontinued
0.7698	Intermediate Similarity	NPD4198	Discontinued
0.7692	Intermediate Similarity	NPD1535	Discovery
0.7692	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7672	Intermediate Similarity	NPD2860	Approved
0.7672	Intermediate Similarity	NPD2859	Approved
0.7656	Intermediate Similarity	NPD1894	Discontinued
0.7634	Intermediate Similarity	NPD1481	Phase 2
0.7619	Intermediate Similarity	NPD2629	Approved
0.7606	Intermediate Similarity	NPD8166	Discontinued
0.7586	Intermediate Similarity	NPD2934	Approved
0.7586	Intermediate Similarity	NPD2933	Approved
0.7586	Intermediate Similarity	NPD5049	Phase 3
0.7576	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7574	Intermediate Similarity	NPD3268	Approved
0.7571	Intermediate Similarity	NPD2935	Discontinued
0.7569	Intermediate Similarity	NPD6799	Approved
0.7552	Intermediate Similarity	NPD3887	Approved
0.7536	Intermediate Similarity	NPD4340	Discontinued
0.7521	Intermediate Similarity	NPD5909	Discontinued
0.7518	Intermediate Similarity	NPD2353	Approved
0.7518	Intermediate Similarity	NPD2355	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD9493	Approved
0.7481	Intermediate Similarity	NPD4136	Approved
0.7481	Intermediate Similarity	NPD4135	Approved
0.7481	Intermediate Similarity	NPD4106	Approved
0.748	Intermediate Similarity	NPD1358	Approved
0.7479	Intermediate Similarity	NPD3020	Approved
0.7462	Intermediate Similarity	NPD4105	Approved
0.7462	Intermediate Similarity	NPD4102	Approved
0.746	Intermediate Similarity	NPD5535	Approved
0.7445	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7434	Intermediate Similarity	NPD7075	Discontinued
0.7413	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7405	Intermediate Similarity	NPD5305	Approved
0.7405	Intermediate Similarity	NPD5306	Approved
0.7391	Intermediate Similarity	NPD6663	Approved
0.7388	Intermediate Similarity	NPD1283	Approved
0.7383	Intermediate Similarity	NPD6599	Discontinued
0.7376	Intermediate Similarity	NPD2799	Discontinued
0.736	Intermediate Similarity	NPD3022	Approved
0.736	Intermediate Similarity	NPD3021	Approved
0.7353	Intermediate Similarity	NPD5736	Approved
0.7351	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7339	Intermediate Similarity	NPD9265	Clinical (unspecified phase)
0.7333	Intermediate Similarity	NPD1203	Approved
0.7333	Intermediate Similarity	NPD987	Approved
0.7315	Intermediate Similarity	NPD3455	Phase 2
0.7293	Intermediate Similarity	NPD4807	Approved
0.7293	Intermediate Similarity	NPD4806	Approved
0.7287	Intermediate Similarity	NPD256	Approved
0.7287	Intermediate Similarity	NPD255	Approved
0.7285	Intermediate Similarity	NPD6801	Discontinued
0.728	Intermediate Similarity	NPD2684	Approved
0.7279	Intermediate Similarity	NPD5647	Approved
0.7273	Intermediate Similarity	NPD3019	Approved
0.7273	Intermediate Similarity	NPD7266	Discontinued
0.7273	Intermediate Similarity	NPD2932	Approved
0.7266	Intermediate Similarity	NPD1241	Discontinued
0.7258	Intermediate Similarity	NPD3134	Approved
0.7254	Intermediate Similarity	NPD7033	Discontinued
0.7254	Intermediate Similarity	NPD4308	Phase 3
0.725	Intermediate Similarity	NPD9495	Approved
0.7246	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.7241	Intermediate Similarity	NPD4110	Phase 3
0.7241	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7239	Intermediate Similarity	NPD3972	Approved
0.7239	Intermediate Similarity	NPD1608	Approved
0.7226	Intermediate Similarity	NPD5204	Approved
0.7214	Intermediate Similarity	NPD825	Approved
0.7214	Intermediate Similarity	NPD826	Approved
0.7206	Intermediate Similarity	NPD3267	Approved
0.7206	Intermediate Similarity	NPD3266	Approved
0.7206	Intermediate Similarity	NPD1164	Approved
0.7188	Intermediate Similarity	NPD7843	Approved
0.7183	Intermediate Similarity	NPD7097	Phase 1
0.7181	Intermediate Similarity	NPD5403	Approved
0.7176	Intermediate Similarity	NPD5536	Phase 2
0.7174	Intermediate Similarity	NPD2614	Approved
0.7174	Intermediate Similarity	NPD6832	Phase 2
0.7164	Intermediate Similarity	NPD1281	Approved
0.7163	Intermediate Similarity	NPD230	Phase 1
0.7162	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD4626	Approved
0.7143	Intermediate Similarity	NPD3882	Suspended
0.7132	Intermediate Similarity	NPD1876	Approved
0.7132	Intermediate Similarity	NPD3225	Approved
0.7123	Intermediate Similarity	NPD3750	Approved
0.7123	Intermediate Similarity	NPD7003	Approved
0.7111	Intermediate Similarity	NPD9717	Approved
0.7109	Intermediate Similarity	NPD969	Suspended
0.7097	Intermediate Similarity	NPD1237	Approved
0.7092	Intermediate Similarity	NPD1240	Approved
0.7092	Intermediate Similarity	NPD2979	Phase 3
0.7086	Intermediate Similarity	NPD7458	Discontinued
0.7083	Intermediate Similarity	NPD4477	Approved
0.7083	Intermediate Similarity	NPD2438	Suspended
0.7083	Intermediate Similarity	NPD4476	Approved
0.7083	Intermediate Similarity	NPD1501	Clinical (unspecified phase)
0.7078	Intermediate Similarity	NPD3817	Phase 2
0.7071	Intermediate Similarity	NPD4621	Approved
0.7071	Intermediate Similarity	NPD2313	Discontinued
0.7071	Intermediate Similarity	NPD4619	Approved
0.7068	Intermediate Similarity	NPD1651	Approved
0.705	Intermediate Similarity	NPD5203	Approved
0.705	Intermediate Similarity	NPD5202	Clinical (unspecified phase)
0.705	Intermediate Similarity	NPD5201	Approved
0.705	Intermediate Similarity	NPD4620	Approved
0.705	Intermediate Similarity	NPD4617	Approved
0.7049	Intermediate Similarity	NPD1238	Approved
0.7047	Intermediate Similarity	NPD5401	Approved
0.7047	Intermediate Similarity	NPD3536	Discontinued
0.7037	Intermediate Similarity	NPD422	Phase 1
0.7034	Intermediate Similarity	NPD2344	Approved
0.7034	Intermediate Similarity	NPD5762	Approved
0.7034	Intermediate Similarity	NPD5763	Approved
0.7031	Intermediate Similarity	NPD2181	Clinical (unspecified phase)
0.7029	Intermediate Similarity	NPD2798	Approved
0.7029	Intermediate Similarity	NPD257	Approved
0.7029	Intermediate Similarity	NPD258	Approved
0.7027	Intermediate Similarity	NPD7440	Discontinued
0.7023	Intermediate Similarity	NPD7157	Approved
0.7015	Intermediate Similarity	NPD17	Approved
0.7008	Intermediate Similarity	NPD6831	Clinical (unspecified phase)
0.7008	Intermediate Similarity	NPD9266	Approved
0.7008	Intermediate Similarity	NPD74	Approved
0.7007	Intermediate Similarity	NPD5667	Approved
0.7	Intermediate Similarity	NPD5283	Phase 1
0.7	Intermediate Similarity	NPD2598	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD6273	Approved
0.7	Intermediate Similarity	NPD1432	Clinical (unspecified phase)
0.6993	Remote Similarity	NPD1607	Approved
0.6993	Remote Similarity	NPD6653	Approved
0.6986	Remote Similarity	NPD2897	Discontinued
0.6986	Remote Similarity	NPD2424	Discontinued
0.6986	Remote Similarity	NPD7596	Clinical (unspecified phase)
0.6978	Remote Similarity	NPD9494	Approved
0.6977	Remote Similarity	NPD228	Approved
0.6972	Remote Similarity	NPD4307	Phase 2
0.697	Remote Similarity	NPD694	Clinical (unspecified phase)
0.697	Remote Similarity	NPD9568	Approved
0.6966	Remote Similarity	NPD2240	Approved
0.6966	Remote Similarity	NPD2239	Approved
0.6963	Remote Similarity	NPD3496	Discontinued
0.694	Remote Similarity	NPD4196	Clinical (unspecified phase)
0.694	Remote Similarity	NPD5691	Approved
0.694	Remote Similarity	NPD5585	Approved
0.6939	Remote Similarity	NPD2976	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD9267	Approved
0.6929	Remote Similarity	NPD9263	Approved
0.6929	Remote Similarity	NPD9264	Approved
0.6928	Remote Similarity	NPD4380	Phase 2
0.6923	Remote Similarity	NPD1933	Approved
0.6923	Remote Similarity	NPD555	Phase 2
0.6923	Remote Similarity	NPD4868	Clinical (unspecified phase)
0.6918	Remote Similarity	NPD1550	Clinical (unspecified phase)
0.6918	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6918	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.6918	Remote Similarity	NPD6800	Clinical (unspecified phase)
0.6917	Remote Similarity	NPD5122	Clinical (unspecified phase)
0.6911	Remote Similarity	NPD2066	Phase 3
0.6908	Remote Similarity	NPD4003	Phase 3
0.6906	Remote Similarity	NPD2788	Approved
0.6901	Remote Similarity	NPD8032	Phase 2
0.6901	Remote Similarity	NPD259	Phase 1
0.6897	Remote Similarity	NPD1510	Phase 2
0.6892	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6889	Remote Similarity	NPD5846	Approved
0.6889	Remote Similarity	NPD6516	Phase 2
0.6883	Remote Similarity	NPD7411	Suspended
0.688	Remote Similarity	NPD6647	Phase 2
0.6879	Remote Similarity	NPD3027	Phase 3
0.6879	Remote Similarity	NPD5163	Phase 2
0.6875	Remote Similarity	NPD7184	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD2182	Approved
0.6871	Remote Similarity	NPD1549	Phase 2
0.6871	Remote Similarity	NPD970	Clinical (unspecified phase)
0.6866	Remote Similarity	NPD1759	Phase 1
0.6859	Remote Similarity	NPD5402	Approved
0.6857	Remote Similarity	NPD3661	Approved
0.6857	Remote Similarity	NPD3663	Approved
0.6857	Remote Similarity	NPD3662	Phase 3
0.6857	Remote Similarity	NPD3664	Approved
0.6855	Remote Similarity	NPD3028	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