NPASS Compound

Structure

NPC185 OpenBabel07101718312D 37 40 0 0 1 0 0 0 0 0999 V2000 2.9855 2.6396 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2424 3.3087 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9641 -3.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9641 -3.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4067 -1.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4067 0.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0032 1.9292 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3872 1.7953 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0563 2.5385 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5388 -0.5000 0.0000 C 0 0 2 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 -0.5909 2.0032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 0.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3301 -2.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0345 2.3305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 2 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 1.7321 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2601 1.2601 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1962 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5388 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9000 2.9543 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3435 1.3795 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2111 0.9511 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 25 1 0 0 0 0 2 25 1 0 0 0 0 3 26 1 0 0 0 0 4 26 1 0 0 0 0 5 27 1 0 0 0 0 9 10 1 0 0 0 0 9 16 2 0 0 0 0 10 20 1 0 0 0 0 11 12 2 0 0 0 0 11 21 1 0 0 0 0 12 25 1 0 0 0 0 13 17 1 0 0 0 0 13 18 1 0 0 0 0 14 19 1 0 0 0 0 14 27 1 0 0 0 0 15 22 1 0 0 0 0 15 28 1 0 0 0 0 16 17 1 0 0 0 0 16 26 1 0 0 0 0 17 29 1 6 0 0 0 18 24 1 0 0 0 0 18 31 2 0 0 0 0 19 23 1 0 0 0 0 19 32 1 1 0 0 0 20 27 1 1 0 0 0 20 29 1 0 0 0 0 21 30 1 0 0 0 0 21 33 2 0 0 0 0 22 29 1 0 0 0 0 22 34 2 0 0 0 0 23 28 1 6 0 0 0 23 30 1 0 0 0 0 24 26 1 0 0 0 0 24 35 1 6 0 0 0 25 36 1 0 0 0 0 27 28 1 1 0 0 0 28 6 1 6 0 0 0 29 7 1 6 0 0 0 30 8 1 6 0 0 0 30 37 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	516.31
Volume:	541.559
LogP:	2.255
LogD:	1.438
LogS:	-4.255
# Rotatable Bonds:	4
TPSA:	132.13
# H-Bond Aceptor:	7
# H-Bond Donor:	4
# Rings:	4
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.334
Synthetic Accessibility Score:	5.347
Fsp3:	0.767
Lipinski Rule-of-5:	Accepted
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:	-4.958
MDCK Permeability:	1.3317421689862385e-05
Pgp-inhibitor:	0.71
Pgp-substrate:	0.038
Human Intestinal Absorption (HIA):	0.056
20% Bioavailability (F20%):	0.778
30% Bioavailability (F30%):	0.119

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.805
Plasma Protein Binding (PPB):	63.013153076171875%
Volume Distribution (VD):	0.412
Pgp-substrate:	21.48306655883789%

ADMET: Metabolism

CYP1A2-inhibitor:	0.004
CYP1A2-substrate:	0.123
CYP2C19-inhibitor:	0.027
CYP2C19-substrate:	0.79
CYP2C9-inhibitor:	0.041
CYP2C9-substrate:	0.743
CYP2D6-inhibitor:	0.006
CYP2D6-substrate:	0.139
CYP3A4-inhibitor:	0.773
CYP3A4-substrate:	0.407

ADMET: Excretion

Clearance (CL):	3.384
Half-life (T1/2):	0.621

ADMET: Toxicity

hERG Blockers:	0.013
Human Hepatotoxicity (H-HT):	0.187
Drug-inuced Liver Injury (DILI):	0.22
AMES Toxicity:	0.032
Rat Oral Acute Toxicity:	0.931
Maximum Recommended Daily Dose:	0.907
Skin Sensitization:	0.176
Carcinogencity:	0.877
Eye Corrosion:	0.003
Eye Irritation:	0.016
Respiratory Toxicity:	0.733

Download Data

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

Natural Product: NPC185

Natural Product ID:	NPC185
*Common Name:**	3-Epi-Isocucurbitacin D
IUPAC Name:	(3R,8S,9R,10R,13R,14S,16R,17R)-17-[(E,2R)-2,6-dihydroxy-6-methyl-3-oxohept-4-en-2-yl]-3,16-dihydroxy-4,4,9,13,14-pentamethyl-3,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthrene-2,11-dione
Synonyms:	3-Epi-Isocucurbitacin D
Standard InCHIKey:	ALPSEMFPAVSKJO-WCGKEEAASA-N
Standard InCHI:	InChI=1S/C30H44O7/c1-25(2,36)12-11-21(33)30(8,37)23-19(32)14-27(5)20-10-9-16-17(13-18(31)24(35)26(16,3)4)29(20,7)22(34)15-28(23,27)6/h9,11-12,17,19-20,23-24,32,35-37H,10,13-15H2,1-8H3/b12-11+/t17-,19-,20+,23+,24+,27+,28-,29+,30+/m1/s1
SMILES:	CC(C)(/C=C/C(=O)[C@@](C)([C@H]1[C@@H](C[C@@]2(C)[C@@H]3CC=C4[C@@H](CC(=O)[C@@H](C4(C)C)O)[C@]3(C)C(=O)C[C@]12C)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2022241
PubChem CID:	57384018
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001686] Cucurbitacins

*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
NPO32449	eleaocarpus chinensis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22239601]

☑ 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	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	39.0	nM	PMID[523944]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	>	10000.0	nM	PMID[523944]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	718.0	nM	PMID[523945]

☑ 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 NPC185 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	195
0.1-0.2	1227
0.2-0.3	4493
0.3-0.4	9720
0.4-0.5	12203
0.5-0.6	7336
0.6-0.7	5408
0.7-0.8	1862
0.8-0.85	170
0.85-0.9	70
0.9-0.95	10
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9592	High Similarity	NPC87351
0.9495	High Similarity	NPC311612
0.9412	High Similarity	NPC214644
0.93	High Similarity	NPC111323
0.9118	High Similarity	NPC257353
0.9	High Similarity	NPC144956
0.8922	High Similarity	NPC249187
0.8922	High Similarity	NPC247957
0.8835	High Similarity	NPC137657
0.8824	High Similarity	NPC473424
0.8824	High Similarity	NPC477915
0.8807	High Similarity	NPC471854
0.88	High Similarity	NPC18509
0.8788	High Similarity	NPC472932
0.8776	High Similarity	NPC233118
0.8762	High Similarity	NPC295244
0.875	High Similarity	NPC149047
0.8704	High Similarity	NPC108721
0.8704	High Similarity	NPC73300
0.87	High Similarity	NPC249954
0.8667	High Similarity	NPC83744
0.8667	High Similarity	NPC477916
0.8667	High Similarity	NPC475060
0.8667	High Similarity	NPC220229
0.8667	High Similarity	NPC165873
0.8654	High Similarity	NPC209502
0.8654	High Similarity	NPC72255
0.8654	High Similarity	NPC204833
0.8627	High Similarity	NPC154072
0.8627	High Similarity	NPC287833
0.8627	High Similarity	NPC474720
0.8611	High Similarity	NPC100267
0.8611	High Similarity	NPC475524
0.86	High Similarity	NPC259286
0.8586	High Similarity	NPC472930
0.8585	High Similarity	NPC177064
0.8585	High Similarity	NPC329417
0.8585	High Similarity	NPC217201
0.8585	High Similarity	NPC65941
0.8571	High Similarity	NPC319077
0.8571	High Similarity	NPC97202
0.8571	High Similarity	NPC296945
0.8571	High Similarity	NPC302607
0.8571	High Similarity	NPC202167
0.8571	High Similarity	NPC49958
0.8571	High Similarity	NPC214264
0.8571	High Similarity	NPC150531
0.8571	High Similarity	NPC60681
0.8571	High Similarity	NPC171137
0.8571	High Similarity	NPC152695
0.8571	High Similarity	NPC48010
0.8571	High Similarity	NPC50692
0.8571	High Similarity	NPC260268
0.8571	High Similarity	NPC476027
0.8571	High Similarity	NPC48733
0.8571	High Similarity	NPC85829
0.8559	High Similarity	NPC311554
0.8559	High Similarity	NPC257457
0.8558	High Similarity	NPC26478
0.8558	High Similarity	NPC191892
0.8545	High Similarity	NPC148458
0.8529	High Similarity	NPC147954
0.8529	High Similarity	NPC197386
0.8519	High Similarity	NPC472928
0.8515	High Similarity	NPC471463
0.8515	High Similarity	NPC49371
0.8505	High Similarity	NPC11710
0.85	High Similarity	NPC8993
0.85	High Similarity	NPC292793
0.8491	Intermediate Similarity	NPC44063
0.8485	Intermediate Similarity	NPC475806
0.8485	Intermediate Similarity	NPC185936
0.8485	Intermediate Similarity	NPC168027
0.8485	Intermediate Similarity	NPC472978
0.8469	Intermediate Similarity	NPC477943
0.8469	Intermediate Similarity	NPC310010
0.8469	Intermediate Similarity	NPC326627
0.8469	Intermediate Similarity	NPC76879
0.8469	Intermediate Similarity	NPC1015
0.8469	Intermediate Similarity	NPC31985
0.8469	Intermediate Similarity	NPC2983
0.8469	Intermediate Similarity	NPC474245
0.8462	Intermediate Similarity	NPC185530
0.8462	Intermediate Similarity	NPC204450
0.8462	Intermediate Similarity	NPC195290
0.8447	Intermediate Similarity	NPC51370
0.844	Intermediate Similarity	NPC147180
0.844	Intermediate Similarity	NPC221144
0.844	Intermediate Similarity	NPC264634
0.8416	Intermediate Similarity	NPC180950
0.8416	Intermediate Similarity	NPC271195
0.84	Intermediate Similarity	NPC69454
0.84	Intermediate Similarity	NPC474736
0.8384	Intermediate Similarity	NPC320026
0.8381	Intermediate Similarity	NPC236390
0.8381	Intermediate Similarity	NPC251017
0.8365	Intermediate Similarity	NPC163372
0.8365	Intermediate Similarity	NPC302537
0.835	Intermediate Similarity	NPC103051
0.8349	Intermediate Similarity	NPC43775
0.8333	Intermediate Similarity	NPC472941
0.8333	Intermediate Similarity	NPC456
0.8333	Intermediate Similarity	NPC192428
0.8333	Intermediate Similarity	NPC2766
0.8319	Intermediate Similarity	NPC472933
0.8318	Intermediate Similarity	NPC475294
0.8318	Intermediate Similarity	NPC472925
0.8317	Intermediate Similarity	NPC472977
0.8317	Intermediate Similarity	NPC196485
0.8317	Intermediate Similarity	NPC245972
0.8317	Intermediate Similarity	NPC299100
0.8317	Intermediate Similarity	NPC474690
0.8317	Intermediate Similarity	NPC472976
0.8304	Intermediate Similarity	NPC239273
0.8304	Intermediate Similarity	NPC472934
0.8302	Intermediate Similarity	NPC75531
0.8302	Intermediate Similarity	NPC149124
0.8302	Intermediate Similarity	NPC235889
0.83	Intermediate Similarity	NPC473998
0.83	Intermediate Similarity	NPC63748
0.8286	Intermediate Similarity	NPC308726
0.8286	Intermediate Similarity	NPC136289
0.8286	Intermediate Similarity	NPC119601
0.8286	Intermediate Similarity	NPC293753
0.8283	Intermediate Similarity	NPC473999
0.8283	Intermediate Similarity	NPC309603
0.8283	Intermediate Similarity	NPC472973
0.8273	Intermediate Similarity	NPC207251
0.8273	Intermediate Similarity	NPC71348
0.8269	Intermediate Similarity	NPC83709
0.8269	Intermediate Similarity	NPC15390
0.8269	Intermediate Similarity	NPC110149
0.8265	Intermediate Similarity	NPC475740
0.8265	Intermediate Similarity	NPC58063
0.8257	Intermediate Similarity	NPC76084
0.8257	Intermediate Similarity	NPC235077
0.8252	Intermediate Similarity	NPC474938
0.8252	Intermediate Similarity	NPC107243
0.8252	Intermediate Similarity	NPC126815
0.8252	Intermediate Similarity	NPC474785
0.8252	Intermediate Similarity	NPC43747
0.8246	Intermediate Similarity	NPC109973
0.8235	Intermediate Similarity	NPC37646
0.8235	Intermediate Similarity	NPC272617
0.8235	Intermediate Similarity	NPC173875
0.8235	Intermediate Similarity	NPC473170
0.8235	Intermediate Similarity	NPC318282
0.8235	Intermediate Similarity	NPC469995
0.8235	Intermediate Similarity	NPC174948
0.823	Intermediate Similarity	NPC329736
0.8224	Intermediate Similarity	NPC181265
0.8224	Intermediate Similarity	NPC166607
0.8224	Intermediate Similarity	NPC51452
0.8218	Intermediate Similarity	NPC474807
0.8218	Intermediate Similarity	NPC472942
0.8198	Intermediate Similarity	NPC317210
0.8198	Intermediate Similarity	NPC472929
0.819	Intermediate Similarity	NPC81530
0.819	Intermediate Similarity	NPC476240
0.819	Intermediate Similarity	NPC476223
0.819	Intermediate Similarity	NPC224720
0.8182	Intermediate Similarity	NPC328539
0.8173	Intermediate Similarity	NPC166745
0.8173	Intermediate Similarity	NPC114274
0.8173	Intermediate Similarity	NPC10364
0.8173	Intermediate Similarity	NPC235464
0.8165	Intermediate Similarity	NPC258543
0.8165	Intermediate Similarity	NPC241927
0.8163	Intermediate Similarity	NPC474732
0.8163	Intermediate Similarity	NPC94666
0.8163	Intermediate Similarity	NPC31564
0.8163	Intermediate Similarity	NPC327115
0.8163	Intermediate Similarity	NPC469994
0.8163	Intermediate Similarity	NPC51014
0.8163	Intermediate Similarity	NPC145879
0.8163	Intermediate Similarity	NPC474733
0.8163	Intermediate Similarity	NPC474778
0.8163	Intermediate Similarity	NPC20688
0.8158	Intermediate Similarity	NPC61520
0.8155	Intermediate Similarity	NPC117133
0.8155	Intermediate Similarity	NPC305483
0.8155	Intermediate Similarity	NPC473164
0.8155	Intermediate Similarity	NPC96859
0.8155	Intermediate Similarity	NPC243525
0.8155	Intermediate Similarity	NPC328162
0.8155	Intermediate Similarity	NPC3772
0.8155	Intermediate Similarity	NPC40765
0.8155	Intermediate Similarity	NPC328371
0.8148	Intermediate Similarity	NPC144459
0.8148	Intermediate Similarity	NPC43285
0.8148	Intermediate Similarity	NPC58370
0.8142	Intermediate Similarity	NPC472927
0.8137	Intermediate Similarity	NPC111015
0.8131	Intermediate Similarity	NPC160843
0.8125	Intermediate Similarity	NPC326542
0.8119	Intermediate Similarity	NPC272746
0.8113	Intermediate Similarity	NPC234892
0.8103	Intermediate Similarity	NPC222688
0.81	Intermediate Similarity	NPC32830
0.81	Intermediate Similarity	NPC472475

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 NPC185 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	169
0.1-0.2	1465
0.2-0.3	3905
0.3-0.4	2447
0.4-0.5	681
0.5-0.6	158
0.6-0.7	157
0.7-0.8	87
0.8-0.85	54
0.85-0.9	21
0.9-0.95	6
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.92	High Similarity	NPD5211	Phase 2
0.902	High Similarity	NPD5141	Approved
0.9	High Similarity	NPD5286	Approved
0.9	High Similarity	NPD4696	Approved
0.9	High Similarity	NPD5285	Approved
0.898	High Similarity	NPD4629	Approved
0.898	High Similarity	NPD5210	Approved
0.8824	High Similarity	NPD5225	Approved
0.8824	High Similarity	NPD4633	Approved
0.8824	High Similarity	NPD5224	Approved
0.8824	High Similarity	NPD5226	Approved
0.88	High Similarity	NPD4755	Approved
0.8738	High Similarity	NPD5175	Approved
0.8738	High Similarity	NPD5174	Approved
0.8725	High Similarity	NPD5223	Approved
0.8627	High Similarity	NPD4700	Approved
0.8585	High Similarity	NPD6881	Approved
0.8585	High Similarity	NPD6899	Approved
0.8519	High Similarity	NPD6650	Approved
0.8519	High Similarity	NPD6649	Approved
0.8515	High Similarity	NPD5220	Clinical (unspecified phase)
0.8515	High Similarity	NPD5222	Approved
0.8515	High Similarity	NPD5221	Approved
0.8491	Intermediate Similarity	NPD5697	Approved
0.8485	Intermediate Similarity	NPD6079	Approved
0.8469	Intermediate Similarity	NPD4753	Phase 2
0.8431	Intermediate Similarity	NPD5173	Approved
0.8426	Intermediate Similarity	NPD7102	Approved
0.8426	Intermediate Similarity	NPD6883	Approved
0.8426	Intermediate Similarity	NPD7290	Approved
0.8411	Intermediate Similarity	NPD4730	Approved
0.8411	Intermediate Similarity	NPD4729	Approved
0.8396	Intermediate Similarity	NPD6675	Approved
0.8396	Intermediate Similarity	NPD7128	Approved
0.8396	Intermediate Similarity	NPD5739	Approved
0.8396	Intermediate Similarity	NPD6402	Approved
0.8349	Intermediate Similarity	NPD6847	Approved
0.8349	Intermediate Similarity	NPD6617	Approved
0.8349	Intermediate Similarity	NPD6869	Approved
0.8349	Intermediate Similarity	NPD8130	Phase 1
0.8333	Intermediate Similarity	NPD6013	Approved
0.8333	Intermediate Similarity	NPD6373	Approved
0.8333	Intermediate Similarity	NPD4697	Phase 3
0.8333	Intermediate Similarity	NPD6012	Approved
0.8333	Intermediate Similarity	NPD6014	Approved
0.8333	Intermediate Similarity	NPD6372	Approved
0.8283	Intermediate Similarity	NPD5328	Approved
0.8273	Intermediate Similarity	NPD8297	Approved
0.8273	Intermediate Similarity	NPD6882	Approved
0.8257	Intermediate Similarity	NPD5250	Approved
0.8257	Intermediate Similarity	NPD5248	Approved
0.8257	Intermediate Similarity	NPD5249	Phase 3
0.8257	Intermediate Similarity	NPD5247	Approved
0.8257	Intermediate Similarity	NPD5251	Approved
0.8257	Intermediate Similarity	NPD4634	Approved
0.8241	Intermediate Similarity	NPD6011	Approved
0.8241	Intermediate Similarity	NPD7320	Approved
0.8241	Intermediate Similarity	NPD5128	Approved
0.8224	Intermediate Similarity	NPD4767	Approved
0.8224	Intermediate Similarity	NPD4768	Approved
0.8208	Intermediate Similarity	NPD4754	Approved
0.8182	Intermediate Similarity	NPD5215	Approved
0.8182	Intermediate Similarity	NPD5216	Approved
0.8182	Intermediate Similarity	NPD5217	Approved
0.8173	Intermediate Similarity	NPD5696	Approved
0.8148	Intermediate Similarity	NPD5701	Approved
0.8091	Intermediate Similarity	NPD5135	Approved
0.8091	Intermediate Similarity	NPD5134	Clinical (unspecified phase)
0.8091	Intermediate Similarity	NPD5169	Approved
0.8077	Intermediate Similarity	NPD6084	Phase 2
0.8077	Intermediate Similarity	NPD6083	Phase 2
0.8061	Intermediate Similarity	NPD5329	Approved
0.8039	Intermediate Similarity	NPD4202	Approved
0.8018	Intermediate Similarity	NPD5127	Approved
0.798	Intermediate Similarity	NPD5690	Phase 2
0.798	Intermediate Similarity	NPD3618	Phase 1
0.7959	Intermediate Similarity	NPD4197	Approved
0.7959	Intermediate Similarity	NPD3666	Approved
0.7959	Intermediate Similarity	NPD3665	Phase 1
0.7959	Intermediate Similarity	NPD3133	Approved
0.7959	Intermediate Similarity	NPD4786	Approved
0.7876	Intermediate Similarity	NPD4632	Approved
0.7857	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.7845	Intermediate Similarity	NPD7100	Approved
0.7845	Intermediate Similarity	NPD7101	Approved
0.7826	Intermediate Similarity	NPD7115	Discovery
0.7807	Intermediate Similarity	NPD5167	Approved
0.7778	Intermediate Similarity	NPD6054	Approved
0.7778	Intermediate Similarity	NPD5091	Approved
0.7759	Intermediate Similarity	NPD6335	Approved
0.7755	Intermediate Similarity	NPD3667	Approved
0.7755	Intermediate Similarity	NPD4221	Approved
0.7755	Intermediate Similarity	NPD4223	Phase 3
0.7748	Intermediate Similarity	NPD5168	Approved
0.7739	Intermediate Similarity	NPD6274	Approved
0.7714	Intermediate Similarity	NPD5695	Phase 3
0.7672	Intermediate Similarity	NPD6009	Approved
0.7672	Intermediate Similarity	NPD6317	Approved
0.7647	Intermediate Similarity	NPD6370	Approved
0.7627	Intermediate Similarity	NPD6319	Approved
0.7624	Intermediate Similarity	NPD5279	Phase 3
0.7624	Intermediate Similarity	NPD4694	Approved
0.7624	Intermediate Similarity	NPD3574	Clinical (unspecified phase)
0.7624	Intermediate Similarity	NPD5280	Approved
0.7607	Intermediate Similarity	NPD6313	Approved
0.7607	Intermediate Similarity	NPD6314	Approved
0.7563	Intermediate Similarity	NPD6016	Approved
0.7563	Intermediate Similarity	NPD6015	Approved
0.7563	Intermediate Similarity	NPD6291	Clinical (unspecified phase)
0.7524	Intermediate Similarity	NPD6399	Phase 3
0.7521	Intermediate Similarity	NPD7492	Approved
0.75	Intermediate Similarity	NPD5988	Approved
0.75	Intermediate Similarity	NPD4788	Approved
0.7479	Intermediate Similarity	NPD6059	Approved
0.7459	Intermediate Similarity	NPD6616	Approved
0.7451	Intermediate Similarity	NPD4689	Approved
0.7451	Intermediate Similarity	NPD4688	Approved
0.7451	Intermediate Similarity	NPD5205	Approved
0.7451	Intermediate Similarity	NPD4690	Approved
0.7451	Intermediate Similarity	NPD4138	Approved
0.7451	Intermediate Similarity	NPD4693	Phase 3
0.7449	Intermediate Similarity	NPD4195	Approved
0.7438	Intermediate Similarity	NPD7604	Phase 2
0.7436	Intermediate Similarity	NPD6868	Approved
0.7429	Intermediate Similarity	NPD5284	Approved
0.7429	Intermediate Similarity	NPD5281	Approved
0.7417	Intermediate Similarity	NPD5983	Phase 2
0.7417	Intermediate Similarity	NPD6909	Approved
0.7417	Intermediate Similarity	NPD6908	Approved
0.7411	Intermediate Similarity	NPD6008	Approved
0.7404	Intermediate Similarity	NPD6673	Approved
0.7404	Intermediate Similarity	NPD6080	Approved
0.7404	Intermediate Similarity	NPD6904	Approved
0.7398	Intermediate Similarity	NPD7078	Approved
0.7374	Intermediate Similarity	NPD4695	Discontinued
0.7339	Intermediate Similarity	NPD7736	Approved
0.7317	Intermediate Similarity	NPD6336	Discontinued
0.7308	Intermediate Similarity	NPD5737	Approved
0.7308	Intermediate Similarity	NPD6672	Approved
0.7282	Intermediate Similarity	NPD7146	Approved
0.7282	Intermediate Similarity	NPD6409	Approved
0.7282	Intermediate Similarity	NPD4623	Approved
0.7282	Intermediate Similarity	NPD5330	Approved
0.7282	Intermediate Similarity	NPD4519	Discontinued
0.7282	Intermediate Similarity	NPD7521	Approved
0.7282	Intermediate Similarity	NPD7334	Approved
0.7282	Intermediate Similarity	NPD6684	Approved
0.7273	Intermediate Similarity	NPD7640	Approved
0.7273	Intermediate Similarity	NPD7639	Approved
0.7264	Intermediate Similarity	NPD5693	Phase 1
0.7264	Intermediate Similarity	NPD7515	Phase 2
0.7255	Intermediate Similarity	NPD3668	Phase 3
0.7222	Intermediate Similarity	NPD6356	Clinical (unspecified phase)
0.7212	Intermediate Similarity	NPD4751	Clinical (unspecified phase)
0.7193	Intermediate Similarity	NPD6614	Approved
0.7184	Intermediate Similarity	NPD5363	Approved
0.7182	Intermediate Similarity	NPD7638	Approved
0.7172	Intermediate Similarity	NPD3617	Approved
0.717	Intermediate Similarity	NPD5785	Approved
0.7143	Intermediate Similarity	NPD6903	Approved
0.7143	Intermediate Similarity	NPD3701	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD7513	Clinical (unspecified phase)
0.712	Intermediate Similarity	NPD8293	Discontinued
0.7115	Intermediate Similarity	NPD6098	Approved
0.7107	Intermediate Similarity	NPD4522	Approved
0.7103	Intermediate Similarity	NPD5694	Approved
0.7103	Intermediate Similarity	NPD6050	Approved
0.7043	Intermediate Similarity	NPD6412	Phase 2
0.7041	Intermediate Similarity	NPD7339	Approved
0.7041	Intermediate Similarity	NPD6942	Approved
0.7037	Intermediate Similarity	NPD5133	Approved
0.7034	Intermediate Similarity	NPD6053	Discontinued
0.703	Intermediate Similarity	NPD7525	Registered
0.7019	Intermediate Similarity	NPD1696	Phase 3
0.7009	Intermediate Similarity	NPD5692	Phase 3
0.6981	Remote Similarity	NPD4518	Approved
0.6972	Remote Similarity	NPD7748	Approved
0.6952	Remote Similarity	NPD5786	Approved
0.6939	Remote Similarity	NPD4785	Approved
0.6939	Remote Similarity	NPD4784	Approved
0.6937	Remote Similarity	NPD7902	Approved
0.6929	Remote Similarity	NPD6033	Approved
0.6905	Remote Similarity	NPD7507	Approved
0.6893	Remote Similarity	NPD4270	Approved
0.6893	Remote Similarity	NPD4269	Approved
0.6887	Remote Similarity	NPD3573	Approved
0.6875	Remote Similarity	NPD4225	Approved
0.6857	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6852	Remote Similarity	NPD4096	Approved
0.6852	Remote Similarity	NPD5207	Approved
0.6832	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6827	Remote Similarity	NPD5362	Discontinued
0.6822	Remote Similarity	NPD5208	Approved
0.6818	Remote Similarity	NPD6001	Approved
0.6796	Remote Similarity	NPD4139	Approved
0.6796	Remote Similarity	NPD4692	Approved
0.6769	Remote Similarity	NPD7260	Phase 2
0.6759	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD7319	Approved
0.6735	Remote Similarity	NPD4243	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