NPASS Compound

Structure

CID191387 OpenBabel06191715572D 48 53 0 0 1 0 0 0 0 0999 V2000 -3.4390 -3.7928 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1434 -2.1295 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0287 -3.2409 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8997 -4.1663 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6568 2.1156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8307 1.8519 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0287 2.3149 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6531 1.6687 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5333 -3.9853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0916 3.2453 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1159 2.3196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2779 3.6871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9137 -3.2971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3264 1.8358 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4884 3.2033 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0287 -0.4630 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6451 -0.4204 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5443 -0.7491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6451 -1.0410 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0287 -2.3149 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6835 -3.2659 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4760 1.6840 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5126 2.2776 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0287 0.4630 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2268 -0.9260 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0079 -3.4897 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2268 0.9260 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3099 -0.7307 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0549 -1.2328 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4249 0.4630 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9228 -0.8278 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7231 1.7938 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0422 0.3843 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0287 1.3890 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5443 0.7491 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4249 -0.4630 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0549 -0.2286 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8307 -1.8519 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2043 -3.0029 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2594 2.1777 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7218 -4.3703 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0907 2.2357 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 2.2268 -1.8519 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3552 -2.6285 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2313 -2.1134 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7473 0.8682 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5119 0.7588 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 9 1 0 0 0 0 3 20 1 0 0 0 0 4 21 1 0 0 0 0 5 22 1 0 0 0 0 6 34 1 0 0 0 0 7 34 1 0 0 0 0 9 13 1 0 0 0 0 10 11 2 0 0 0 0 10 12 1 0 0 0 0 11 14 1 0 0 0 0 12 15 2 0 0 0 0 13 26 1 0 0 0 0 14 23 2 0 0 0 0 15 23 1 0 0 0 0 16 25 1 0 0 0 0 17 19 1 0 0 0 0 17 37 1 0 0 0 0 18 43 1 0 0 0 0 19 2 1 1 0 0 0 19 29 1 0 0 0 0 20 38 2 0 0 0 0 20 44 1 0 0 0 0 21 39 2 0 0 0 0 21 45 1 0 0 0 0 22 40 2 0 0 0 0 22 48 1 0 0 0 0 23 32 1 0 0 0 0 24 16 1 1 0 0 0 24 27 1 0 0 0 0 24 34 1 0 0 0 0 25 36 1 1 0 0 0 25 44 1 0 0 0 0 26 41 2 0 0 0 0 26 46 1 0 0 0 0 27 30 1 0 0 0 0 27 34 1 1 0 0 0 28 29 1 0 0 0 0 28 31 1 0 0 0 0 28 37 1 1 0 0 0 29 46 1 1 0 0 0 30 35 1 6 0 0 0 30 36 1 0 0 0 0 31 36 1 6 0 0 0 31 45 1 0 0 0 0 32 42 2 0 0 0 0 32 47 1 0 0 0 0 33 35 1 6 0 0 0 33 37 1 0 0 0 0 33 47 1 0 0 0 0 35 8 1 6 0 0 0 35 43 1 0 0 0 0 36 18 1 6 0 0 0 37 48 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	668.32
Volume:	672.77
LogP:	4.804
LogD:	3.252
LogS:	-4.888
# Rotatable Bonds:	13
TPSA:	140.73
# H-Bond Aceptor:	11
# H-Bond Donor:	0
# Rings:	6
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.278
Synthetic Accessibility Score:	6.06
Fsp3:	0.703
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.285
MDCK Permeability:	8.608717325842008e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.017
20% Bioavailability (F20%):	0.197
30% Bioavailability (F30%):	0.134

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.214
Plasma Protein Binding (PPB):	83.8630142211914%
Volume Distribution (VD):	1.836
Pgp-substrate:	11.358521461486816%

ADMET: Metabolism

CYP1A2-inhibitor:	0.03
CYP1A2-substrate:	0.037
CYP2C19-inhibitor:	0.08
CYP2C19-substrate:	0.067
CYP2C9-inhibitor:	0.773
CYP2C9-substrate:	0.028
CYP2D6-inhibitor:	0.099
CYP2D6-substrate:	0.04
CYP3A4-inhibitor:	0.677
CYP3A4-substrate:	0.347

ADMET: Excretion

Clearance (CL):	3.203
Half-life (T1/2):	0.756

ADMET: Toxicity

hERG Blockers:	0.823
Human Hepatotoxicity (H-HT):	0.994
Drug-inuced Liver Injury (DILI):	0.971
AMES Toxicity:	0.006
Rat Oral Acute Toxicity:	0.169
Maximum Recommended Daily Dose:	0.034
Skin Sensitization:	0.209
Carcinogencity:	0.008
Eye Corrosion:	0.003
Eye Irritation:	0.015
Respiratory Toxicity:	0.888

Download Data

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

Natural Product: NPC191387

Natural Product ID:	NPC191387
*Common Name:**	Euphorbiaproliferin J
IUPAC Name:	n.a.
Synonyms:	Euphorbiaproliferin J
Standard InCHIKey:	OWSWMLHRWAIDBR-FKTGJEKHSA-N
Standard InCHI:	InChI=1S/C37H48O11/c1-9-13-26(41)46-29-19(2)17-37(48-22(5)40)28(29)31(45-21(4)39)36-18-43-35(8,33(37)47-32(42)23-14-11-10-12-15-23)30(36)27-24(34(27,6)7)16-25(36)44-20(3)38/h10-12,14-15,19,24-25,27-31,33H,9,13,16-18H2,1-8H3/t19-,24-,25+,27-,28+,29-,30-,31+,33+,35+,36+,37+/m0/s1
SMILES:	CCCC(=O)O[C@H]1[C@@H](C)C[C@]2([C@H]1[C@H]([C@]13CO[C@](C)([C@@H]3[C@@H]3[C@H](C[C@H]1OC(=O)C)C3(C)C)[C@H]2OC(=O)c1ccccc1)OC(=O)C)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1927839
PubChem CID:	56601464
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0002995] Pentacarboxylic acids and derivatives

*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
NPO12377	Euphorbia prolifera	Species	Euphorbiaceae	Eukaryota	Roots	Kunming, Yunnan Province, China	2010-JUL	PMID[21928782]
NPO12377	Euphorbia prolifera	Species	Euphorbiaceae	Eukaryota	n.a.	root	n.a.	PMID[21928782]
NPO12377	Euphorbia prolifera	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22560584]
NPO12377	Euphorbia prolifera	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[7775985]
NPO12377	Euphorbia prolifera	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12377	Euphorbia prolifera	Species	Euphorbiaceae	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
Others	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT519	Cell Line	SH-SY5Y	Homo sapiens	Activity	=	79.8	%	PMID[479262]
NPT519	Cell Line	SH-SY5Y	Homo sapiens	Activity	=	89.2	%	PMID[479262]
NPT519	Cell Line	SH-SY5Y	Homo sapiens	Activity	=	104.2	%	PMID[479262]

☑ 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 NPC191387 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	385
0.1-0.2	1285
0.2-0.3	2460
0.3-0.4	5794
0.4-0.5	11841
0.5-0.6	15910
0.6-0.7	4015
0.7-0.8	795
0.8-0.85	161
0.85-0.9	47
0.9-0.95	2
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC131966
0.9259	High Similarity	NPC298547
0.9259	High Similarity	NPC324898
0.9259	High Similarity	NPC134937
0.9197	High Similarity	NPC327511
0.9197	High Similarity	NPC205305
0.9191	High Similarity	NPC149401
0.9191	High Similarity	NPC279637
0.913	High Similarity	NPC53361
0.913	High Similarity	NPC121268
0.9104	High Similarity	NPC475508
0.9028	High Similarity	NPC125033
0.8865	High Similarity	NPC187566
0.8841	High Similarity	NPC153617
0.8819	High Similarity	NPC312393
0.8819	High Similarity	NPC240115
0.8803	High Similarity	NPC192658
0.8803	High Similarity	NPC475135
0.8794	High Similarity	NPC162613
0.8794	High Similarity	NPC87934
0.8777	High Similarity	NPC291638
0.8777	High Similarity	NPC472577
0.8777	High Similarity	NPC195647
0.8777	High Similarity	NPC17877
0.8777	High Similarity	NPC66761
0.8777	High Similarity	NPC200154
0.8759	High Similarity	NPC470278
0.8732	High Similarity	NPC266374
0.8725	High Similarity	NPC290683
0.8725	High Similarity	NPC475638
0.8725	High Similarity	NPC475548
0.8723	High Similarity	NPC9905
0.8716	High Similarity	NPC472658
0.8716	High Similarity	NPC472657
0.8716	High Similarity	NPC471135
0.8705	High Similarity	NPC474608
0.8696	High Similarity	NPC233860
0.869	High Similarity	NPC478263
0.8686	High Similarity	NPC147561
0.8684	High Similarity	NPC55744
0.8681	High Similarity	NPC34943
0.8662	High Similarity	NPC43241
0.8662	High Similarity	NPC473758
0.8662	High Similarity	NPC251294
0.8662	High Similarity	NPC476094
0.8662	High Similarity	NPC473085
0.8662	High Similarity	NPC147880
0.8662	High Similarity	NPC473081
0.8662	High Similarity	NPC473060
0.8662	High Similarity	NPC473109
0.8662	High Similarity	NPC200592
0.8662	High Similarity	NPC473112
0.8662	High Similarity	NPC473613
0.8662	High Similarity	NPC211137
0.8662	High Similarity	NPC48017
0.8662	High Similarity	NPC184747
0.8662	High Similarity	NPC4341
0.8652	High Similarity	NPC475373
0.8633	High Similarity	NPC472248
0.863	High Similarity	NPC327031
0.8621	High Similarity	NPC478264
0.8621	High Similarity	NPC125882
0.8601	High Similarity	NPC16912
0.86	High Similarity	NPC326235
0.86	High Similarity	NPC70344
0.86	High Similarity	NPC323001
0.8592	High Similarity	NPC214550
0.8592	High Similarity	NPC210591
0.8592	High Similarity	NPC276652
0.8592	High Similarity	NPC475652
0.8592	High Similarity	NPC473301
0.8581	High Similarity	NPC96308
0.8571	High Similarity	NPC472250
0.8571	High Similarity	NPC28836
0.8571	High Similarity	NPC76103
0.8562	High Similarity	NPC48599
0.8562	High Similarity	NPC473602
0.8562	High Similarity	NPC209592
0.8562	High Similarity	NPC20255
0.8561	High Similarity	NPC239358
0.8553	High Similarity	NPC309991
0.8553	High Similarity	NPC471138
0.8553	High Similarity	NPC326328
0.8553	High Similarity	NPC323356
0.8543	High Similarity	NPC318447
0.8543	High Similarity	NPC322048
0.8531	High Similarity	NPC171207
0.8531	High Similarity	NPC475660
0.8531	High Similarity	NPC183270
0.8531	High Similarity	NPC97667
0.8531	High Similarity	NPC477904
0.8531	High Similarity	NPC90614
0.8523	High Similarity	NPC283875
0.8523	High Similarity	NPC233581
0.8523	High Similarity	NPC22571
0.8523	High Similarity	NPC469648
0.8523	High Similarity	NPC469647
0.8523	High Similarity	NPC138641
0.8523	High Similarity	NPC145649
0.8521	High Similarity	NPC283375
0.8521	High Similarity	NPC183122
0.8514	High Similarity	NPC476173
0.8511	High Similarity	NPC475262
0.8511	High Similarity	NPC290833
0.8511	High Similarity	NPC265459
0.8511	High Similarity	NPC79699
0.8511	High Similarity	NPC473216
0.8511	High Similarity	NPC473399
0.8511	High Similarity	NPC270364
0.8503	High Similarity	NPC473760
0.8493	Intermediate Similarity	NPC92867
0.8493	Intermediate Similarity	NPC311825
0.8483	Intermediate Similarity	NPC153214
0.8483	Intermediate Similarity	NPC177340
0.8483	Intermediate Similarity	NPC147217
0.8483	Intermediate Similarity	NPC191082
0.8483	Intermediate Similarity	NPC95449
0.8483	Intermediate Similarity	NPC139067
0.8483	Intermediate Similarity	NPC82467
0.8483	Intermediate Similarity	NPC270498
0.8483	Intermediate Similarity	NPC246480
0.8483	Intermediate Similarity	NPC475429
0.8483	Intermediate Similarity	NPC473673
0.8472	Intermediate Similarity	NPC97947
0.8472	Intermediate Similarity	NPC242355
0.8472	Intermediate Similarity	NPC27377
0.8472	Intermediate Similarity	NPC291599
0.8472	Intermediate Similarity	NPC473654
0.8472	Intermediate Similarity	NPC41481
0.8472	Intermediate Similarity	NPC472576
0.8472	Intermediate Similarity	NPC87448
0.8472	Intermediate Similarity	NPC118080
0.8451	Intermediate Similarity	NPC194769
0.8451	Intermediate Similarity	NPC202729
0.8451	Intermediate Similarity	NPC285221
0.844	Intermediate Similarity	NPC311492
0.8435	Intermediate Similarity	NPC477095
0.8429	Intermediate Similarity	NPC472394
0.8429	Intermediate Similarity	NPC238370
0.8429	Intermediate Similarity	NPC233692
0.8425	Intermediate Similarity	NPC95810
0.8425	Intermediate Similarity	NPC188865
0.8425	Intermediate Similarity	NPC476974
0.8425	Intermediate Similarity	NPC470231
0.8425	Intermediate Similarity	NPC51314
0.8425	Intermediate Similarity	NPC472569
0.8425	Intermediate Similarity	NPC67777
0.8425	Intermediate Similarity	NPC472573
0.8425	Intermediate Similarity	NPC163719
0.8425	Intermediate Similarity	NPC11685
0.8425	Intermediate Similarity	NPC70716
0.8425	Intermediate Similarity	NPC25768
0.8425	Intermediate Similarity	NPC57628
0.8425	Intermediate Similarity	NPC125106
0.8425	Intermediate Similarity	NPC95265
0.8425	Intermediate Similarity	NPC472570
0.8414	Intermediate Similarity	NPC183540
0.8403	Intermediate Similarity	NPC100913
0.8403	Intermediate Similarity	NPC275592
0.8403	Intermediate Similarity	NPC472547
0.8392	Intermediate Similarity	NPC86772
0.8392	Intermediate Similarity	NPC27721
0.8389	Intermediate Similarity	NPC475561
0.8389	Intermediate Similarity	NPC31829
0.8389	Intermediate Similarity	NPC475417
0.8378	Intermediate Similarity	NPC132652
0.8367	Intermediate Similarity	NPC158663
0.8367	Intermediate Similarity	NPC171525
0.8367	Intermediate Similarity	NPC476973
0.8367	Intermediate Similarity	NPC472575
0.8367	Intermediate Similarity	NPC473088
0.8367	Intermediate Similarity	NPC472572
0.8367	Intermediate Similarity	NPC184817
0.8367	Intermediate Similarity	NPC471104
0.8367	Intermediate Similarity	NPC470159
0.8367	Intermediate Similarity	NPC70403
0.8367	Intermediate Similarity	NPC472568
0.8367	Intermediate Similarity	NPC29704
0.8367	Intermediate Similarity	NPC200471
0.8367	Intermediate Similarity	NPC177940
0.8367	Intermediate Similarity	NPC174982
0.8367	Intermediate Similarity	NPC470157
0.8367	Intermediate Similarity	NPC472571
0.8367	Intermediate Similarity	NPC96903
0.8367	Intermediate Similarity	NPC469349
0.8357	Intermediate Similarity	NPC72915
0.8356	Intermediate Similarity	NPC477096
0.8356	Intermediate Similarity	NPC477094
0.8356	Intermediate Similarity	NPC163087
0.8355	Intermediate Similarity	NPC11410
0.8333	Intermediate Similarity	NPC472398
0.8333	Intermediate Similarity	NPC325805
0.8333	Intermediate Similarity	NPC272523
0.8323	Intermediate Similarity	NPC478124
0.8322	Intermediate Similarity	NPC472374
0.8322	Intermediate Similarity	NPC472372
0.8322	Intermediate Similarity	NPC472551
0.8322	Intermediate Similarity	NPC472545
0.8311	Intermediate Similarity	NPC474935
0.831	Intermediate Similarity	NPC471911

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 NPC191387 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	290
0.1-0.2	805
0.2-0.3	1653
0.3-0.4	3116
0.4-0.5	2182
0.5-0.6	957
0.6-0.7	139
0.7-0.8	8
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
0.8	Intermediate Similarity	NPD7236	Approved
0.7963	Intermediate Similarity	NPD7799	Discontinued
0.7857	Intermediate Similarity	NPD7239	Suspended
0.7817	Intermediate Similarity	NPD6007	Clinical (unspecified phase)
0.7643	Intermediate Similarity	NPD7457	Clinical (unspecified phase)
0.7415	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.7407	Intermediate Similarity	NPD7057	Phase 3
0.7407	Intermediate Similarity	NPD7058	Phase 2
0.7353	Intermediate Similarity	NPD2181	Clinical (unspecified phase)
0.7178	Intermediate Similarity	NPD5761	Phase 2
0.7178	Intermediate Similarity	NPD5760	Phase 2
0.7126	Intermediate Similarity	NPD8127	Discontinued
0.7122	Intermediate Similarity	NPD6858	Approved
0.7122	Intermediate Similarity	NPD7094	Approved
0.7086	Intermediate Similarity	NPD7961	Discontinued
0.708	Intermediate Similarity	NPD2182	Approved
0.7076	Intermediate Similarity	NPD8470	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD6273	Approved
0.7063	Intermediate Similarity	NPD7741	Discontinued
0.7052	Intermediate Similarity	NPD6765	Approved
0.7052	Intermediate Similarity	NPD6764	Approved
0.7029	Intermediate Similarity	NPD8407	Phase 2
0.6989	Remote Similarity	NPD8055	Clinical (unspecified phase)
0.6987	Remote Similarity	NPD6003	Clinical (unspecified phase)
0.6987	Remote Similarity	NPD6004	Phase 3
0.6987	Remote Similarity	NPD6002	Phase 3
0.6987	Remote Similarity	NPD6006	Clinical (unspecified phase)
0.6987	Remote Similarity	NPD6005	Phase 3
0.6974	Remote Similarity	NPD6663	Approved
0.6966	Remote Similarity	NPD3412	Clinical (unspecified phase)
0.6962	Remote Similarity	NPD4628	Phase 3
0.6954	Remote Similarity	NPD8368	Discontinued
0.6954	Remote Similarity	NPD7685	Pre-registration
0.6949	Remote Similarity	NPD8424	Clinical (unspecified phase)
0.6949	Remote Similarity	NPD8434	Phase 2
0.6928	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6905	Remote Similarity	NPD5537	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD2629	Approved
0.6893	Remote Similarity	NPD6784	Approved
0.6893	Remote Similarity	NPD6785	Approved
0.6871	Remote Similarity	NPD6287	Discontinued
0.6842	Remote Similarity	NPD7008	Discontinued
0.6821	Remote Similarity	NPD5736	Approved
0.6812	Remote Similarity	NPD6685	Approved
0.6797	Remote Similarity	NPD3764	Approved
0.6788	Remote Similarity	NPD164	Approved
0.6772	Remote Similarity	NPD5763	Approved
0.6772	Remote Similarity	NPD5762	Approved
0.6753	Remote Similarity	NPD8032	Phase 2
0.6741	Remote Similarity	NPD1238	Approved
0.6736	Remote Similarity	NPD4198	Discontinued
0.6714	Remote Similarity	NPD6831	Clinical (unspecified phase)
0.6709	Remote Similarity	NPD2438	Suspended
0.6702	Remote Similarity	NPD7497	Discontinued
0.6687	Remote Similarity	NPD7028	Phase 2
0.6685	Remote Similarity	NPD8360	Approved
0.6685	Remote Similarity	NPD8435	Approved
0.6685	Remote Similarity	NPD8361	Approved
0.6667	Remote Similarity	NPD2067	Discontinued
0.6667	Remote Similarity	NPD7055	Discontinued
0.6667	Remote Similarity	NPD7819	Suspended
0.6667	Remote Similarity	NPD5951	Approved
0.6646	Remote Similarity	NPD8166	Discontinued
0.6644	Remote Similarity	NPD7610	Discontinued
0.6627	Remote Similarity	NPD6591	Clinical (unspecified phase)
0.6623	Remote Similarity	NPD1876	Approved
0.6622	Remote Similarity	NPD5125	Phase 3
0.6622	Remote Similarity	NPD5126	Approved
0.6604	Remote Similarity	NPD7137	Phase 2
0.6594	Remote Similarity	NPD5765	Approved
0.6588	Remote Similarity	NPD4967	Phase 2
0.6588	Remote Similarity	NPD4966	Approved
0.6588	Remote Similarity	NPD4965	Approved
0.6587	Remote Similarity	NPD6599	Discontinued
0.6575	Remote Similarity	NPD4230	Clinical (unspecified phase)
0.6573	Remote Similarity	NPD6912	Phase 3
0.6562	Remote Similarity	NPD7702	Clinical (unspecified phase)
0.6561	Remote Similarity	NPD6355	Discontinued
0.6558	Remote Similarity	NPD6832	Phase 2
0.6552	Remote Similarity	NPD690	Clinical (unspecified phase)
0.6545	Remote Similarity	NPD7314	Clinical (unspecified phase)
0.6543	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6536	Remote Similarity	NPD5740	Clinical (unspecified phase)
0.6536	Remote Similarity	NPD6085	Phase 2
0.6527	Remote Similarity	NPD7458	Discontinued
0.6519	Remote Similarity	NPD6653	Approved
0.6512	Remote Similarity	NPD6234	Discontinued
0.6509	Remote Similarity	NPD37	Approved
0.6506	Remote Similarity	NPD6980	Clinical (unspecified phase)
0.6503	Remote Similarity	NPD7274	Clinical (unspecified phase)
0.6497	Remote Similarity	NPD4140	Approved
0.6497	Remote Similarity	NPD2979	Phase 3
0.6486	Remote Similarity	NPD7009	Phase 2
0.6485	Remote Similarity	NPD7004	Clinical (unspecified phase)
0.6485	Remote Similarity	NPD2533	Approved
0.6485	Remote Similarity	NPD2532	Approved
0.6485	Remote Similarity	NPD2534	Approved
0.6484	Remote Similarity	NPD8150	Discontinued
0.6475	Remote Similarity	NPD5738	Clinical (unspecified phase)
0.6474	Remote Similarity	NPD5494	Approved
0.6471	Remote Similarity	NPD8485	Approved
0.6471	Remote Similarity	NPD7096	Clinical (unspecified phase)
0.646	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6458	Remote Similarity	NPD1609	Clinical (unspecified phase)
0.6453	Remote Similarity	NPD7075	Discontinued
0.6447	Remote Similarity	NPD5327	Phase 3
0.6443	Remote Similarity	NPD5585	Approved
0.6442	Remote Similarity	NPD7003	Approved
0.6442	Remote Similarity	NPD4109	Clinical (unspecified phase)
0.6442	Remote Similarity	NPD4110	Phase 3
0.6438	Remote Similarity	NPD2799	Discontinued
0.6438	Remote Similarity	NPD3748	Approved
0.6438	Remote Similarity	NPD4766	Approved
0.6438	Remote Similarity	NPD7305	Phase 1
0.6437	Remote Similarity	NPD7199	Phase 2
0.6433	Remote Similarity	NPD7713	Phase 3
0.6409	Remote Similarity	NPD8312	Approved
0.6409	Remote Similarity	NPD8313	Approved
0.6404	Remote Similarity	NPD5844	Phase 1
0.64	Remote Similarity	NPD7163	Clinical (unspecified phase)
0.6398	Remote Similarity	NPD2935	Discontinued
0.6389	Remote Similarity	NPD4141	Clinical (unspecified phase)
0.6387	Remote Similarity	NPD7084	Phase 3
0.6384	Remote Similarity	NPD7473	Discontinued
0.6383	Remote Similarity	NPD6008	Approved
0.6382	Remote Similarity	NPD6637	Approved
0.6382	Remote Similarity	NPD3972	Approved
0.638	Remote Similarity	NPD7421	Clinical (unspecified phase)
0.6377	Remote Similarity	NPD7798	Approved
0.6376	Remote Similarity	NPD9545	Approved
0.6375	Remote Similarity	NPD2567	Approved
0.6375	Remote Similarity	NPD2569	Approved
0.6368	Remote Similarity	NPD8486	Clinical (unspecified phase)
0.6364	Remote Similarity	NPD7184	Clinical (unspecified phase)
0.6364	Remote Similarity	NPD3094	Phase 2
0.6358	Remote Similarity	NPD2346	Discontinued
0.6357	Remote Similarity	NPD1931	Clinical (unspecified phase)
0.6357	Remote Similarity	NPD1930	Approved
0.6357	Remote Similarity	NPD1929	Approved
0.6352	Remote Similarity	NPD5735	Approved
0.6348	Remote Similarity	NPD7228	Approved
0.6345	Remote Similarity	NPD8462	Phase 1
0.6344	Remote Similarity	NPD7879	Clinical (unspecified phase)
0.6333	Remote Similarity	NPD3025	Approved
0.6333	Remote Similarity	NPD3024	Approved
0.6331	Remote Similarity	NPD3226	Approved
0.6331	Remote Similarity	NPD5808	Clinical (unspecified phase)
0.6325	Remote Similarity	NPD6799	Approved
0.6325	Remote Similarity	NPD6143	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD1281	Approved
0.6316	Remote Similarity	NPD6801	Discontinued
0.6312	Remote Similarity	NPD6353	Approved
0.6307	Remote Similarity	NPD6232	Discontinued
0.6303	Remote Similarity	NPD6190	Approved
0.6301	Remote Similarity	NPD7768	Phase 2
0.6301	Remote Similarity	NPD4868	Clinical (unspecified phase)
0.6299	Remote Similarity	NPD5667	Approved
0.6298	Remote Similarity	NPD6559	Discontinued
0.6296	Remote Similarity	NPD2796	Approved
0.6294	Remote Similarity	NPD4380	Phase 2
0.6291	Remote Similarity	NPD17	Approved
0.6289	Remote Similarity	NPD4307	Phase 2
0.6287	Remote Similarity	NPD8389	Clinical (unspecified phase)
0.6279	Remote Similarity	NPD8455	Phase 2
0.6277	Remote Similarity	NPD1989	Approved
0.6275	Remote Similarity	NPD7507	Approved
0.6259	Remote Similarity	NPD2066	Phase 3
0.6258	Remote Similarity	NPD6362	Approved
0.6257	Remote Similarity	NPD6386	Approved
0.6257	Remote Similarity	NPD6385	Approved
0.6257	Remote Similarity	NPD6873	Phase 2
0.6257	Remote Similarity	NPD7893	Clinical (unspecified phase)
0.625	Remote Similarity	NPD1202	Approved
0.625	Remote Similarity	NPD3023	Approved
0.625	Remote Similarity	NPD230	Phase 1
0.625	Remote Similarity	NPD1899	Clinical (unspecified phase)
0.625	Remote Similarity	NPD3026	Approved
0.6243	Remote Similarity	NPD3817	Phase 2
0.6243	Remote Similarity	NPD5402	Approved
0.6243	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6242	Remote Similarity	NPD3750	Approved
0.6241	Remote Similarity	NPD6647	Phase 2
0.6237	Remote Similarity	NPD8397	Clinical (unspecified phase)
0.6236	Remote Similarity	NPD7997	Clinical (unspecified phase)
0.6234	Remote Similarity	NPD4359	Approved
0.6233	Remote Similarity	NPD8297	Approved
0.6225	Remote Similarity	NPD8033	Approved
0.6225	Remote Similarity	NPD5691	Approved
0.622	Remote Similarity	NPD970	Clinical (unspecified phase)
0.6215	Remote Similarity	NPD7315	Approved
0.6213	Remote Similarity	NPD5403	Approved
0.6213	Remote Similarity	NPD920	Approved
0.6209	Remote Similarity	NPD4807	Approved
0.6209	Remote Similarity	NPD7240	Approved
0.6209	Remote Similarity	NPD4806	Approved
0.6205	Remote Similarity	NPD3887	Approved
0.6205	Remote Similarity	NPD7999	Approved
0.6197	Remote Similarity	NPD5909	Discontinued
0.6196	Remote Similarity	NPD2531	Phase 2
0.6196	Remote Similarity	NPD5406	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