NPASS Compound

Structure

CID257240 OpenBabel06191716062D 31 34 0 0 1 0 0 0 0 0999 V2000 -3.9476 -1.4724 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2360 0.9918 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2170 -1.7287 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5116 -2.1533 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3448 -0.5675 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2363 0.3958 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9983 -0.5043 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9908 -1.4410 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2352 1.2352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1831 -1.1564 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1407 2.1309 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1853 0.0237 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5315 -1.0432 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0274 -1.3325 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5116 1.2352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7469 0.7236 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6762 -0.7555 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5677 0.2078 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 0.7236 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8318 0.4034 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6447 -0.3285 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3215 -0.4164 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4563 -0.1799 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5116 -0.5116 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7308 2.9000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8956 1.0946 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5392 1.7744 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2708 -1.3845 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7292 0.6388 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5085 0.1116 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 7 1 0 0 0 0 2 12 1 0 0 0 0 3 13 1 0 0 0 0 4 14 1 0 0 0 0 5 23 1 0 0 0 0 6 23 1 0 0 0 0 7 12 2 0 0 0 0 8 14 1 0 0 0 0 9 15 2 0 0 0 0 10 13 2 0 0 0 0 10 24 1 0 0 0 0 11 15 1 0 0 0 0 11 26 1 0 0 0 0 12 22 1 0 0 0 0 13 21 1 0 0 0 0 14 24 1 1 0 0 0 15 19 1 0 0 0 0 16 9 1 1 0 0 0 16 18 1 0 0 0 0 16 20 1 0 0 0 0 17 8 1 6 0 0 0 17 18 1 0 0 0 0 17 23 1 0 0 0 0 18 23 1 6 0 0 0 19 25 1 6 0 0 0 19 27 1 0 0 0 0 20 24 1 0 0 0 0 20 28 2 0 0 0 0 21 25 1 6 0 0 0 21 31 1 0 0 0 0 22 29 2 0 0 0 0 22 31 1 0 0 0 0 24 25 1 6 0 0 0 25 30 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	430.24
Volume:	446.289
LogP:	3.253
LogD:	2.758
LogS:	-3.851
# Rotatable Bonds:	4
TPSA:	104.06
# H-Bond Aceptor:	6
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.361
Synthetic Accessibility Score:	6.426
Fsp3:	0.68
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.97
MDCK Permeability:	1.783216248441022e-05
Pgp-inhibitor:	0.985
Pgp-substrate:	0.663
Human Intestinal Absorption (HIA):	0.021
20% Bioavailability (F20%):	0.69
30% Bioavailability (F30%):	0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.681
Plasma Protein Binding (PPB):	82.07325744628906%
Volume Distribution (VD):	1.196
Pgp-substrate:	9.399494171142578%

ADMET: Metabolism

CYP1A2-inhibitor:	0.039
CYP1A2-substrate:	0.254
CYP2C19-inhibitor:	0.118
CYP2C19-substrate:	0.779
CYP2C9-inhibitor:	0.341
CYP2C9-substrate:	0.063
CYP2D6-inhibitor:	0.022
CYP2D6-substrate:	0.083
CYP3A4-inhibitor:	0.567
CYP3A4-substrate:	0.529

ADMET: Excretion

Clearance (CL):	6.993
Half-life (T1/2):	0.155

ADMET: Toxicity

hERG Blockers:	0.024
Human Hepatotoxicity (H-HT):	0.539
Drug-inuced Liver Injury (DILI):	0.089
AMES Toxicity:	0.073
Rat Oral Acute Toxicity:	0.897
Maximum Recommended Daily Dose:	0.943
Skin Sensitization:	0.721
Carcinogencity:	0.291
Eye Corrosion:	0.006
Eye Irritation:	0.021
Respiratory Toxicity:	0.983

Download Data

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

Natural Product: NPC257240

Natural Product ID:	NPC257240
*Common Name:**	Ingenol Mebutate
IUPAC Name:	n.a.
Synonyms:	Ingenol Mebutate; PEP-005; Picato
Standard InCHIKey:	VDJHFHXMUKFKET-WDUFCVPESA-N
Standard InCHI:	InChI=1S/C25H34O6/c1-7-12(2)22(29)31-21-13(3)10-24-14(4)8-17-18(23(17,5)6)16(20(24)28)9-15(11-26)19(27)25(21,24)30/h7,9-10,14,16-19,21,26-27,30H,8,11H2,1-6H3/b12-7-/t14-,16+,17-,18+,19-,21+,24+,25+/m1/s1
SMILES:	C/C=C(/C)C(=O)O[C@H]1C(=C[C@]23[C@H](C)C[C@@H]4[C@H]([C@H](C=C(CO)[C@H]([C@]13O)O)C2=O)C4(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1863513
PubChem CID:	6918670
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002875] Tigliane and ingenane diterpenoids

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO13882	Euphorbia grandicornis	Species	Euphorbiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21319774]
NPO13882	Euphorbia grandicornis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27731641]
NPO41583	Xylaria flabelliformis + Aspergillus fischeri	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[32096649]
NPO1853	Euphorbia canariensis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13882	Euphorbia grandicornis	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
EC50	15
Others	20

Activity Type	# Activity
Cell Line	4
Individual Protein	2
NON-MOLECULAR	1
Organism	12
Others	13
Protein Family	1
SINGLE PROTEIN	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell Line	HeLa	Homo sapiens	LC50	=	230000.0	nM	PMID[504452]
NPT165	Cell Line	HeLa	Homo sapiens	LC50	=	230000.0	nM	PMID[504453]
NPT466	Cell Line	U-937	Homo sapiens	CC50	>	200.0	nM	PMID[504456]
NPT25	Cell Line	MT4	Homo sapiens	CC50	>	9300.0	nM	PMID[504457]
NPT881	Individual Protein	Protein kinase C delta	Homo sapiens	EC50	=	4.1	nM	PMID[504452]
NPT2	Others	Unspecified		EC50	=	10.3	nM	PMID[504452]
NPT2	Others	Unspecified		EC50	=	11.2	nM	PMID[504452]
NPT2	Others	Unspecified		EC50	=	8.7	nM	PMID[504452]
NPT35	Others	n.a.		Drug recovery	=	60.0	%	PMID[504452]
NPT35	Others	n.a.		Drug recovery	=	60.0	%	PMID[504453]
NPT2	Others	Unspecified		EC50	=	11.2	nM	PMID[504453]
NPT2	Others	Unspecified		EC50	=	10.3	nM	PMID[504453]
NPT2	Others	Unspecified		EC50	=	8.7	nM	PMID[504453]
NPT881	Individual Protein	Protein kinase C delta	Homo sapiens	EC50	=	4.1	nM	PMID[504453]
NPT2	Others	Unspecified		Ratio CC50/EC50	=	7847.0	n.a.	PMID[504454]
NPT2	Others	Unspecified		Ratio CC50/EC50	=	2.3	n.a.	PMID[504454]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	EC50	=	22900.0	nM	PMID[504454]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	17.0	nM	PMID[504454]
NPT332	Organism	Human immunodeficiency virus type 2 (ISOLATE ROD)	Human immunodeficiency virus type 2 (ISOLATE ROD)	EC50	=	9.0	nM	PMID[504454]
NPT2	Others	Unspecified		Ratio CC50/EC50	=	13451.0	n.a.	PMID[504454]
NPT316	Protein Family	Protein kinase C (PKC)	Homo sapiens	EC50	=	72.5	nM	PMID[504455]
NPT2	Others	Unspecified		Ratio CC50/EC50	>	42.0	n.a.	PMID[504456]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	FC	=	9.7	n.a.	PMID[504456]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	4.8	nM	PMID[504456]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	4.5	nM	PMID[504457]
NPT2	Others	Unspecified		Ratio CC50/EC50	>	2067.0	n.a.	PMID[504457]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	4.2	nM	PMID[504457]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	1.08	%	PMID[504458]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Hit score	=	0.3195	n.a.	PMID[504459]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	10.71	%	PMID[504460]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.1615	%	PMID[504461]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	2.17	%	PMID[504462]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	1.7	%	PMID[504463]

☑ 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 NPC257240 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	1538
0.2-0.3	4993
0.3-0.4	8955
0.4-0.5	14512
0.5-0.6	7569
0.6-0.7	3741
0.7-0.8	1033
0.8-0.85	56
0.85-0.9	8
0.9-0.95	8
0.95-1	23

Similarity Score	Similarity Level	Natural Product ID
0.9712	High Similarity	NPC46269
0.9712	High Similarity	NPC106395
0.9706	High Similarity	NPC477102
0.9619	High Similarity	NPC133677
0.9619	High Similarity	NPC67290
0.9619	High Similarity	NPC138303
0.9615	High Similarity	NPC76550
0.9615	High Similarity	NPC138757
0.9615	High Similarity	NPC123855
0.9612	High Similarity	NPC477103
0.9608	High Similarity	NPC308191
0.9604	High Similarity	NPC179891
0.9333	High Similarity	NPC287311
0.9327	High Similarity	NPC47951
0.8857	High Similarity	NPC475661
0.8857	High Similarity	NPC473488
0.8774	High Similarity	NPC473911
0.8713	High Similarity	NPC261341
0.8585	High Similarity	NPC203659
0.8585	High Similarity	NPC100487
0.8505	High Similarity	NPC243998
0.8491	Intermediate Similarity	NPC110989
0.8426	Intermediate Similarity	NPC26617
0.8421	Intermediate Similarity	NPC477092
0.8396	Intermediate Similarity	NPC86077
0.8396	Intermediate Similarity	NPC225353
0.8333	Intermediate Similarity	NPC475401
0.8333	Intermediate Similarity	NPC223450
0.8319	Intermediate Similarity	NPC234858
0.8319	Intermediate Similarity	NPC154363
0.8319	Intermediate Similarity	NPC471127
0.8318	Intermediate Similarity	NPC475871
0.8318	Intermediate Similarity	NPC475945
0.8302	Intermediate Similarity	NPC150923
0.8291	Intermediate Similarity	NPC472399
0.8246	Intermediate Similarity	NPC10721
0.8246	Intermediate Similarity	NPC475305
0.8241	Intermediate Similarity	NPC474741
0.823	Intermediate Similarity	NPC472400
0.8224	Intermediate Similarity	NPC474747
0.819	Intermediate Similarity	NPC477949
0.819	Intermediate Similarity	NPC157252
0.819	Intermediate Similarity	NPC145182
0.819	Intermediate Similarity	NPC471126
0.819	Intermediate Similarity	NPC471128
0.819	Intermediate Similarity	NPC475885
0.8174	Intermediate Similarity	NPC124676
0.8174	Intermediate Similarity	NPC146280
0.8173	Intermediate Similarity	NPC304886
0.8148	Intermediate Similarity	NPC472755
0.8142	Intermediate Similarity	NPC472757
0.8142	Intermediate Similarity	NPC71889
0.8131	Intermediate Similarity	NPC171759
0.8131	Intermediate Similarity	NPC474742
0.812	Intermediate Similarity	NPC52839
0.812	Intermediate Similarity	NPC472401
0.8113	Intermediate Similarity	NPC141191
0.8103	Intermediate Similarity	NPC236918
0.8103	Intermediate Similarity	NPC156745
0.8087	Intermediate Similarity	NPC156252
0.8087	Intermediate Similarity	NPC475323
0.8077	Intermediate Similarity	NPC470013
0.8077	Intermediate Similarity	NPC470010
0.8077	Intermediate Similarity	NPC477131
0.8077	Intermediate Similarity	NPC167219
0.8077	Intermediate Similarity	NPC323008
0.8077	Intermediate Similarity	NPC198853
0.8077	Intermediate Similarity	NPC262133
0.807	Intermediate Similarity	NPC474872
0.8058	Intermediate Similarity	NPC476705
0.8051	Intermediate Similarity	NPC162009
0.8051	Intermediate Similarity	NPC257017
0.8051	Intermediate Similarity	NPC19464
0.8037	Intermediate Similarity	NPC288876
0.8034	Intermediate Similarity	NPC329080
0.8034	Intermediate Similarity	NPC472759
0.8019	Intermediate Similarity	NPC170143
0.8019	Intermediate Similarity	NPC311904
0.8019	Intermediate Similarity	NPC108475
0.8019	Intermediate Similarity	NPC161493
0.8019	Intermediate Similarity	NPC169205
0.8019	Intermediate Similarity	NPC213947
0.8017	Intermediate Similarity	NPC171905
0.8017	Intermediate Similarity	NPC472397
0.8017	Intermediate Similarity	NPC472758
0.8017	Intermediate Similarity	NPC471125
0.8017	Intermediate Similarity	NPC236999
0.8017	Intermediate Similarity	NPC288679
0.8	Intermediate Similarity	NPC14961
0.8	Intermediate Similarity	NPC67584
0.8	Intermediate Similarity	NPC52044
0.8	Intermediate Similarity	NPC270013
0.8	Intermediate Similarity	NPC220221
0.8	Intermediate Similarity	NPC54737
0.8	Intermediate Similarity	NPC469873
0.8	Intermediate Similarity	NPC36954
0.7982	Intermediate Similarity	NPC124881
0.7981	Intermediate Similarity	NPC475912
0.7966	Intermediate Similarity	NPC470829
0.7966	Intermediate Similarity	NPC473228
0.7965	Intermediate Similarity	NPC475937
0.7965	Intermediate Similarity	NPC260786
0.7965	Intermediate Similarity	NPC96739
0.7965	Intermediate Similarity	NPC475495
0.7965	Intermediate Similarity	NPC317107
0.7965	Intermediate Similarity	NPC174471
0.7965	Intermediate Similarity	NPC474871
0.7965	Intermediate Similarity	NPC158523
0.7963	Intermediate Similarity	NPC474339
0.7963	Intermediate Similarity	NPC472753
0.7963	Intermediate Similarity	NPC477950
0.7963	Intermediate Similarity	NPC164598
0.7961	Intermediate Similarity	NPC473448
0.7949	Intermediate Similarity	NPC5991
0.7949	Intermediate Similarity	NPC255081
0.7949	Intermediate Similarity	NPC5989
0.7949	Intermediate Similarity	NPC471108
0.7949	Intermediate Similarity	NPC22628
0.7949	Intermediate Similarity	NPC275696
0.7946	Intermediate Similarity	NPC273433
0.7944	Intermediate Similarity	NPC221615
0.7931	Intermediate Similarity	NPC471145
0.7931	Intermediate Similarity	NPC471146
0.7925	Intermediate Similarity	NPC230800
0.7925	Intermediate Similarity	NPC213078
0.7925	Intermediate Similarity	NPC18019
0.7925	Intermediate Similarity	NPC24956
0.7925	Intermediate Similarity	NPC476315
0.7925	Intermediate Similarity	NPC185553
0.7925	Intermediate Similarity	NPC279621
0.7917	Intermediate Similarity	NPC473709
0.7917	Intermediate Similarity	NPC473919
0.7917	Intermediate Similarity	NPC144625
0.7917	Intermediate Similarity	NPC145238
0.7909	Intermediate Similarity	NPC472756
0.7909	Intermediate Similarity	NPC220964
0.7909	Intermediate Similarity	NPC475676
0.7909	Intermediate Similarity	NPC146731
0.7909	Intermediate Similarity	NPC309190
0.7909	Intermediate Similarity	NPC296950
0.7905	Intermediate Similarity	NPC65829
0.7905	Intermediate Similarity	NPC474035
0.7905	Intermediate Similarity	NPC81386
0.7895	Intermediate Similarity	NPC477093
0.7895	Intermediate Similarity	NPC215643
0.7895	Intermediate Similarity	NPC17138
0.7895	Intermediate Similarity	NPC475391
0.7895	Intermediate Similarity	NPC317687
0.7895	Intermediate Similarity	NPC89227
0.7895	Intermediate Similarity	NPC265499
0.7895	Intermediate Similarity	NPC473522
0.7895	Intermediate Similarity	NPC35069
0.7895	Intermediate Similarity	NPC101825
0.7895	Intermediate Similarity	NPC170212
0.7895	Intermediate Similarity	NPC475277
0.7895	Intermediate Similarity	NPC151216
0.7895	Intermediate Similarity	NPC258711
0.7895	Intermediate Similarity	NPC221511
0.789	Intermediate Similarity	NPC472754
0.789	Intermediate Similarity	NPC118405
0.7885	Intermediate Similarity	NPC30515
0.7885	Intermediate Similarity	NPC184463
0.7885	Intermediate Similarity	NPC131209
0.7885	Intermediate Similarity	NPC133698
0.7881	Intermediate Similarity	NPC19336
0.7881	Intermediate Similarity	NPC185876
0.7876	Intermediate Similarity	NPC153036
0.787	Intermediate Similarity	NPC280963
0.787	Intermediate Similarity	NPC70865
0.7863	Intermediate Similarity	NPC472760
0.7863	Intermediate Similarity	NPC475372
0.7857	Intermediate Similarity	NPC14862
0.7857	Intermediate Similarity	NPC233379
0.7857	Intermediate Similarity	NPC474664
0.7851	Intermediate Similarity	NPC222307
0.785	Intermediate Similarity	NPC474313
0.785	Intermediate Similarity	NPC40812
0.7833	Intermediate Similarity	NPC129992
0.7833	Intermediate Similarity	NPC473802
0.783	Intermediate Similarity	NPC213698
0.783	Intermediate Similarity	NPC193645
0.783	Intermediate Similarity	NPC275960
0.783	Intermediate Similarity	NPC90121
0.783	Intermediate Similarity	NPC475900
0.783	Intermediate Similarity	NPC170120
0.783	Intermediate Similarity	NPC48803
0.7826	Intermediate Similarity	NPC474937
0.7826	Intermediate Similarity	NPC209058
0.7818	Intermediate Similarity	NPC4620
0.7818	Intermediate Similarity	NPC474165
0.7818	Intermediate Similarity	NPC69171
0.7818	Intermediate Similarity	NPC475873
0.7815	Intermediate Similarity	NPC46570
0.7815	Intermediate Similarity	NPC67569
0.781	Intermediate Similarity	NPC212486
0.781	Intermediate Similarity	NPC469645
0.781	Intermediate Similarity	NPC125674
0.781	Intermediate Similarity	NPC469692
0.781	Intermediate Similarity	NPC475838
0.781	Intermediate Similarity	NPC228451

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 NPC257240 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	272
0.1-0.2	2188
0.2-0.3	3625
0.3-0.4	2022
0.4-0.5	727
0.5-0.6	262
0.6-0.7	45
0.7-0.8	7
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD6371	Approved
0.8426	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.783	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7788	Intermediate Similarity	NPD5785	Approved
0.7619	Intermediate Similarity	NPD6698	Approved
0.7619	Intermediate Similarity	NPD46	Approved
0.7524	Intermediate Similarity	NPD1695	Approved
0.7479	Intermediate Similarity	NPD7115	Discovery
0.7308	Intermediate Similarity	NPD5363	Approved
0.7297	Intermediate Similarity	NPD4225	Approved
0.729	Intermediate Similarity	NPD7838	Discovery
0.7241	Intermediate Similarity	NPD6686	Approved
0.7222	Intermediate Similarity	NPD7983	Approved
0.7091	Intermediate Similarity	NPD5282	Discontinued
0.7019	Intermediate Similarity	NPD4269	Approved
0.7019	Intermediate Similarity	NPD5209	Approved
0.7019	Intermediate Similarity	NPD4270	Approved
0.7018	Intermediate Similarity	NPD5344	Discontinued
0.7	Intermediate Similarity	NPD6053	Discontinued
0.6952	Remote Similarity	NPD5362	Discontinued
0.6923	Remote Similarity	NPD5369	Approved
0.6916	Remote Similarity	NPD5786	Approved
0.688	Remote Similarity	NPD6319	Approved
0.6846	Remote Similarity	NPD7319	Approved
0.6842	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6827	Remote Similarity	NPD4252	Approved
0.6822	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6792	Remote Similarity	NPD7154	Phase 3
0.6783	Remote Similarity	NPD7639	Approved
0.6783	Remote Similarity	NPD7640	Approved
0.6777	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.675	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD7507	Approved
0.6723	Remote Similarity	NPD6412	Phase 2
0.6697	Remote Similarity	NPD4251	Approved
0.6697	Remote Similarity	NPD4250	Approved
0.6696	Remote Similarity	NPD5779	Approved
0.6696	Remote Similarity	NPD7638	Approved
0.6696	Remote Similarity	NPD5778	Approved
0.6667	Remote Similarity	NPD4821	Approved
0.6667	Remote Similarity	NPD4819	Approved
0.6667	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD4632	Approved
0.6667	Remote Similarity	NPD7492	Approved
0.6667	Remote Similarity	NPD4820	Approved
0.6667	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD4822	Approved
0.6638	Remote Similarity	NPD6648	Approved
0.6635	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6615	Remote Similarity	NPD6616	Approved
0.6614	Remote Similarity	NPD6054	Approved
0.6609	Remote Similarity	NPD6084	Phase 2
0.6609	Remote Similarity	NPD6083	Phase 2
0.6607	Remote Similarity	NPD7637	Suspended
0.6606	Remote Similarity	NPD4249	Approved
0.6589	Remote Similarity	NPD7604	Phase 2
0.6585	Remote Similarity	NPD8297	Approved
0.6565	Remote Similarity	NPD7078	Approved
0.6562	Remote Similarity	NPD8513	Phase 3
0.6562	Remote Similarity	NPD8516	Approved
0.6562	Remote Similarity	NPD8517	Approved
0.6562	Remote Similarity	NPD8515	Approved
0.6557	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6542	Remote Similarity	NPD6435	Approved
0.6529	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6529	Remote Similarity	NPD6899	Approved
0.6529	Remote Similarity	NPD6881	Approved
0.6515	Remote Similarity	NPD7736	Approved
0.6512	Remote Similarity	NPD6370	Approved
0.6504	Remote Similarity	NPD6649	Approved
0.6504	Remote Similarity	NPD6650	Approved
0.65	Remote Similarity	NPD7128	Approved
0.65	Remote Similarity	NPD6008	Approved
0.65	Remote Similarity	NPD5739	Approved
0.65	Remote Similarity	NPD6675	Approved
0.65	Remote Similarity	NPD6402	Approved
0.6489	Remote Similarity	NPD8273	Phase 1
0.6484	Remote Similarity	NPD6059	Approved
0.6476	Remote Similarity	NPD4271	Approved
0.6476	Remote Similarity	NPD4268	Approved
0.6475	Remote Similarity	NPD6372	Approved
0.6475	Remote Similarity	NPD6373	Approved
0.6462	Remote Similarity	NPD7642	Approved
0.6457	Remote Similarity	NPD7327	Approved
0.6457	Remote Similarity	NPD7328	Approved
0.6446	Remote Similarity	NPD5697	Approved
0.6439	Remote Similarity	NPD8293	Discontinued
0.6435	Remote Similarity	NPD5695	Phase 3
0.6434	Remote Similarity	NPD7503	Approved
0.6434	Remote Similarity	NPD6015	Approved
0.6434	Remote Similarity	NPD6016	Approved
0.6434	Remote Similarity	NPD8033	Approved
0.6423	Remote Similarity	NPD6883	Approved
0.6423	Remote Similarity	NPD7290	Approved
0.6423	Remote Similarity	NPD7102	Approved
0.6423	Remote Similarity	NPD4634	Approved
0.641	Remote Similarity	NPD5696	Approved
0.6406	Remote Similarity	NPD7516	Approved
0.6404	Remote Similarity	NPD6399	Phase 3
0.6393	Remote Similarity	NPD7320	Approved
0.6389	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6385	Remote Similarity	NPD5988	Approved
0.6378	Remote Similarity	NPD6009	Approved
0.6371	Remote Similarity	NPD6869	Approved
0.6371	Remote Similarity	NPD6847	Approved
0.6371	Remote Similarity	NPD6617	Approved
0.6371	Remote Similarity	NPD8130	Phase 1
0.6364	Remote Similarity	NPD1694	Approved
0.6357	Remote Similarity	NPD8377	Approved
0.6357	Remote Similarity	NPD8294	Approved
0.6355	Remote Similarity	NPD5368	Approved
0.6341	Remote Similarity	NPD6013	Approved
0.6341	Remote Similarity	NPD6014	Approved
0.6341	Remote Similarity	NPD6012	Approved
0.633	Remote Similarity	NPD5331	Approved
0.633	Remote Similarity	NPD5332	Approved
0.632	Remote Similarity	NPD6882	Approved
0.6316	Remote Similarity	NPD6411	Approved
0.6316	Remote Similarity	NPD8074	Phase 3
0.6311	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6311	Remote Similarity	NPD5701	Approved
0.6308	Remote Similarity	NPD8296	Approved
0.6308	Remote Similarity	NPD8380	Approved
0.6308	Remote Similarity	NPD5983	Phase 2
0.6308	Remote Similarity	NPD8335	Approved
0.6308	Remote Similarity	NPD8379	Approved
0.6308	Remote Similarity	NPD8378	Approved
0.6296	Remote Similarity	NPD4790	Discontinued
0.6293	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.627	Remote Similarity	NPD8133	Approved
0.626	Remote Similarity	NPD6011	Approved
0.625	Remote Similarity	NPD7632	Discontinued
0.625	Remote Similarity	NPD7524	Approved
0.625	Remote Similarity	NPD5211	Phase 2
0.6241	Remote Similarity	NPD6336	Discontinued
0.6239	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6239	Remote Similarity	NPD7839	Suspended
0.6212	Remote Similarity	NPD7829	Approved
0.6212	Remote Similarity	NPD8328	Phase 3
0.6212	Remote Similarity	NPD7830	Approved
0.6182	Remote Similarity	NPD6110	Phase 1
0.6174	Remote Similarity	NPD5693	Phase 1
0.6174	Remote Similarity	NPD5284	Approved
0.6174	Remote Similarity	NPD5281	Approved
0.6161	Remote Similarity	NPD7334	Approved
0.6161	Remote Similarity	NPD6684	Approved
0.6161	Remote Similarity	NPD5330	Approved
0.6161	Remote Similarity	NPD7146	Approved
0.6161	Remote Similarity	NPD7521	Approved
0.6161	Remote Similarity	NPD6409	Approved
0.6154	Remote Similarity	NPD5210	Approved
0.6154	Remote Similarity	NPD4629	Approved
0.6148	Remote Similarity	NPD5141	Approved
0.6143	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.614	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.614	Remote Similarity	NPD4753	Phase 2
0.614	Remote Similarity	NPD6101	Approved
0.614	Remote Similarity	NPD5370	Suspended
0.6131	Remote Similarity	NPD7260	Phase 2
0.6126	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6126	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6083	Remote Similarity	NPD4696	Approved
0.6083	Remote Similarity	NPD5285	Approved
0.6083	Remote Similarity	NPD5286	Approved
0.6058	Remote Similarity	NPD5956	Approved
0.6053	Remote Similarity	NPD6903	Approved
0.6053	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.605	Remote Similarity	NPD4755	Approved
0.605	Remote Similarity	NPD7902	Approved
0.6047	Remote Similarity	NPD6274	Approved
0.6036	Remote Similarity	NPD6695	Phase 3
0.6034	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.6031	Remote Similarity	NPD4522	Approved
0.6031	Remote Similarity	NPD7100	Approved
0.6031	Remote Similarity	NPD7101	Approved
0.6029	Remote Similarity	NPD6033	Approved
0.6	Remote Similarity	NPD6904	Approved
0.6	Remote Similarity	NPD6673	Approved
0.6	Remote Similarity	NPD6080	Approved
0.6	Remote Similarity	NPD8451	Approved
0.6	Remote Similarity	NPD7500	Approved
0.5984	Remote Similarity	NPD4633	Approved
0.5984	Remote Similarity	NPD5224	Approved
0.5984	Remote Similarity	NPD5225	Approved
0.5984	Remote Similarity	NPD5226	Approved
0.5983	Remote Similarity	NPD4202	Approved
0.5982	Remote Similarity	NPD3665	Phase 1
0.5982	Remote Similarity	NPD3133	Approved
0.5982	Remote Similarity	NPD3666	Approved
0.5956	Remote Similarity	NPD8448	Approved
0.5954	Remote Similarity	NPD7641	Discontinued
0.5954	Remote Similarity	NPD6335	Approved
0.5952	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.595	Remote Similarity	NPD4700	Approved
0.594	Remote Similarity	NPD8444	Approved
0.594	Remote Similarity	NPD6921	Approved
0.5935	Remote Similarity	NPD5174	Approved
0.5935	Remote Similarity	NPD5175	Approved
0.5932	Remote Similarity	NPD7748	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