NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	500.24
Volume:	510.485
LogP:	3.714
LogD:	2.772
LogS:	-4.31
# Rotatable Bonds:	8
TPSA:	116.2
# H-Bond Aceptor:	8
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.265
Synthetic Accessibility Score:	6.294
Fsp3:	0.643
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:	-4.964
MDCK Permeability:	3.055277556995861e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.016
Human Intestinal Absorption (HIA):	0.032
20% Bioavailability (F20%):	0.993
30% Bioavailability (F30%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.264
Plasma Protein Binding (PPB):	73.69564819335938%
Volume Distribution (VD):	1.88
Pgp-substrate:	17.304889678955078%

ADMET: Metabolism

CYP1A2-inhibitor:	0.072
CYP1A2-substrate:	0.099
CYP2C19-inhibitor:	0.503
CYP2C19-substrate:	0.303
CYP2C9-inhibitor:	0.624
CYP2C9-substrate:	0.029
CYP2D6-inhibitor:	0.213
CYP2D6-substrate:	0.044
CYP3A4-inhibitor:	0.817
CYP3A4-substrate:	0.587

ADMET: Excretion

Clearance (CL):	3.192
Half-life (T1/2):	0.1

ADMET: Toxicity

hERG Blockers:	0.068
Human Hepatotoxicity (H-HT):	0.217
Drug-inuced Liver Injury (DILI):	0.336
AMES Toxicity:	0.681
Rat Oral Acute Toxicity:	0.715
Maximum Recommended Daily Dose:	0.893
Skin Sensitization:	0.763
Carcinogencity:	0.365
Eye Corrosion:	0.023
Eye Irritation:	0.042
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC477102

Natural Product ID:	NPC477102
*Common Name:**	[(1S,4S,5R,6R,9S,10R,12R)-6-acetyloxy-7-(acetyloxymethyl)-5-hydroxy-3,11,11-trimethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] (Z)-2-methylbut-2-enoate
IUPAC Name:	[(1S,4S,5R,6R,9S,10R,12R)-6-acetyloxy-7-(acetyloxymethyl)-5-hydroxy-3,11,11-trimethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] (Z)-2-methylbut-2-enoate
Synonyms:	Ingenol 3-Angelate 5,20-Diacetate
Standard InCHIKey:	XLPLYIPUTHRBCU-JODHMPKJSA-N
Standard InCHI:	InChI=1S/C28H36O8/c1-8-14(2)25(32)36-23-15(3)12-27-10-9-20-21(26(20,6)7)19(22(27)31)11-18(13-34-16(4)29)24(28(23,27)33)35-17(5)30/h8,11-12,19-21,23-24,33H,9-10,13H2,1-7H3/b14-8-/t19-,20+,21-,23-,24+,27+,28+/m0/s1
SMILES:	C/C=C(/C)\C(=O)O[C@H]1C(=C[C@@]23[C@@]1([C@@H](C(=C[C@H](C2=O)[C@H]4[C@H](C4(C)C)CC3)COC(=O)C)OC(=O)C)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	45269949
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0001986] Tricarboxylic 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
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	aerial parts	Yuanjiang, Yunnan Province, China	2008-APR	PMID[19438253]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	Stems	n.a.	n.a.	PMID[30730729]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12595	Euphorbia royleana	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
IC50	1
Others	3

Activity Type	# Activity
Others	4

Target ID	Target Type	Target Name	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	IC50	=	0.61	ug/ml	PMID[19438253]
NPT2	Others	Unspecified	Inhibition	=	38.7	%	PMID[19438253]
NPT2	Others	Unspecified	Inhibition	=	97.9	%	PMID[19438253]
NPT2	Others	Unspecified	Inhibition	=	100	%	PMID[19438253]

☑ 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 NPC477102 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	262
0.1-0.2	1579
0.2-0.3	5195
0.3-0.4	9236
0.4-0.5	14327
0.5-0.6	7534
0.6-0.7	3522
0.7-0.8	977
0.8-0.85	29
0.85-0.9	4
0.9-0.95	28
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
0.9901	High Similarity	NPC477103
0.9706	High Similarity	NPC257240
0.9429	High Similarity	NPC106395
0.9429	High Similarity	NPC46269
0.934	High Similarity	NPC67290
0.934	High Similarity	NPC133677
0.934	High Similarity	NPC138303
0.9333	High Similarity	NPC76550
0.9333	High Similarity	NPC138757
0.9333	High Similarity	NPC123855
0.932	High Similarity	NPC308191
0.9314	High Similarity	NPC179891
0.9238	High Similarity	NPC287311
0.9048	High Similarity	NPC47951
0.9038	High Similarity	NPC473911
0.8679	High Similarity	NPC26617
0.8585	High Similarity	NPC473488
0.8585	High Similarity	NPC475661
0.8491	Intermediate Similarity	NPC203659
0.8431	Intermediate Similarity	NPC261341
0.8411	Intermediate Similarity	NPC223450
0.8407	Intermediate Similarity	NPC475401
0.8396	Intermediate Similarity	NPC110989
0.8333	Intermediate Similarity	NPC477092
0.8319	Intermediate Similarity	NPC475305
0.8318	Intermediate Similarity	NPC100487
0.8318	Intermediate Similarity	NPC474741
0.8302	Intermediate Similarity	NPC225353
0.8246	Intermediate Similarity	NPC288679
0.8241	Intermediate Similarity	NPC243998
0.8224	Intermediate Similarity	NPC475945
0.8224	Intermediate Similarity	NPC475871
0.8208	Intermediate Similarity	NPC474742
0.8205	Intermediate Similarity	NPC472399
0.8198	Intermediate Similarity	NPC475495
0.8155	Intermediate Similarity	NPC477131
0.8131	Intermediate Similarity	NPC474747
0.8131	Intermediate Similarity	NPC86077
0.8125	Intermediate Similarity	NPC473522
0.8125	Intermediate Similarity	NPC475277
0.8125	Intermediate Similarity	NPC477093
0.8125	Intermediate Similarity	NPC475391
0.812	Intermediate Similarity	NPC257017
0.812	Intermediate Similarity	NPC162009
0.8113	Intermediate Similarity	NPC280963
0.8103	Intermediate Similarity	NPC145182
0.8103	Intermediate Similarity	NPC471126
0.8103	Intermediate Similarity	NPC471128
0.8103	Intermediate Similarity	NPC157252
0.8095	Intermediate Similarity	NPC213947
0.8095	Intermediate Similarity	NPC108475
0.8095	Intermediate Similarity	NPC170143
0.8095	Intermediate Similarity	NPC477949
0.8087	Intermediate Similarity	NPC124676
0.8087	Intermediate Similarity	NPC146280
0.8083	Intermediate Similarity	NPC236999
0.8077	Intermediate Similarity	NPC67584
0.807	Intermediate Similarity	NPC471127
0.807	Intermediate Similarity	NPC234858
0.807	Intermediate Similarity	NPC154363
0.8058	Intermediate Similarity	NPC476300
0.8056	Intermediate Similarity	NPC472755
0.8053	Intermediate Similarity	NPC474937
0.8037	Intermediate Similarity	NPC474339
0.8037	Intermediate Similarity	NPC164598
0.8037	Intermediate Similarity	NPC171759
0.8037	Intermediate Similarity	NPC150923
0.8036	Intermediate Similarity	NPC96739
0.8036	Intermediate Similarity	NPC174471
0.8036	Intermediate Similarity	NPC474871
0.8036	Intermediate Similarity	NPC260786
0.8034	Intermediate Similarity	NPC472401
0.8034	Intermediate Similarity	NPC52839
0.8	Intermediate Similarity	NPC475323
0.8	Intermediate Similarity	NPC471145
0.8	Intermediate Similarity	NPC213078
0.8	Intermediate Similarity	NPC471146
0.8	Intermediate Similarity	NPC10721
0.7983	Intermediate Similarity	NPC144625
0.7982	Intermediate Similarity	NPC474872
0.7982	Intermediate Similarity	NPC472756
0.7982	Intermediate Similarity	NPC472400
0.7981	Intermediate Similarity	NPC470010
0.7981	Intermediate Similarity	NPC323008
0.7981	Intermediate Similarity	NPC262133
0.7981	Intermediate Similarity	NPC470013
0.7981	Intermediate Similarity	NPC198853
0.7981	Intermediate Similarity	NPC167219
0.7966	Intermediate Similarity	NPC19464
0.7965	Intermediate Similarity	NPC89227
0.7965	Intermediate Similarity	NPC265499
0.7965	Intermediate Similarity	NPC101825
0.7965	Intermediate Similarity	NPC17138
0.7965	Intermediate Similarity	NPC151216
0.7965	Intermediate Similarity	NPC221511
0.7965	Intermediate Similarity	NPC215643
0.7965	Intermediate Similarity	NPC170212
0.7963	Intermediate Similarity	NPC149371
0.7963	Intermediate Similarity	NPC183571
0.7963	Intermediate Similarity	NPC472754
0.7961	Intermediate Similarity	NPC133698
0.7949	Intermediate Similarity	NPC475885
0.7931	Intermediate Similarity	NPC471125
0.7931	Intermediate Similarity	NPC171905
0.7931	Intermediate Similarity	NPC475372
0.7931	Intermediate Similarity	NPC472397
0.7931	Intermediate Similarity	NPC472758
0.7925	Intermediate Similarity	NPC161493
0.7925	Intermediate Similarity	NPC311904
0.7917	Intermediate Similarity	NPC222307
0.7909	Intermediate Similarity	NPC54737
0.7909	Intermediate Similarity	NPC9303
0.7909	Intermediate Similarity	NPC16313
0.7905	Intermediate Similarity	NPC52044
0.7905	Intermediate Similarity	NPC475900
0.7905	Intermediate Similarity	NPC304886
0.7905	Intermediate Similarity	NPC36954
0.7899	Intermediate Similarity	NPC129992
0.7899	Intermediate Similarity	NPC473802
0.7895	Intermediate Similarity	NPC472757
0.7895	Intermediate Similarity	NPC71889
0.7895	Intermediate Similarity	NPC209058
0.789	Intermediate Similarity	NPC475873
0.789	Intermediate Similarity	NPC4620
0.789	Intermediate Similarity	NPC124881
0.789	Intermediate Similarity	NPC69171
0.789	Intermediate Similarity	NPC474165
0.7881	Intermediate Similarity	NPC470829
0.7881	Intermediate Similarity	NPC473228
0.787	Intermediate Similarity	NPC47880
0.787	Intermediate Similarity	NPC477950
0.787	Intermediate Similarity	NPC472753
0.7869	Intermediate Similarity	NPC13071
0.7864	Intermediate Similarity	NPC51004
0.7863	Intermediate Similarity	NPC236918
0.7863	Intermediate Similarity	NPC275696
0.7863	Intermediate Similarity	NPC22628
0.7863	Intermediate Similarity	NPC5989
0.7863	Intermediate Similarity	NPC255081
0.7863	Intermediate Similarity	NPC471108
0.7863	Intermediate Similarity	NPC312536
0.7863	Intermediate Similarity	NPC156745
0.7863	Intermediate Similarity	NPC5991
0.7857	Intermediate Similarity	NPC273433
0.7857	Intermediate Similarity	NPC59489
0.7857	Intermediate Similarity	NPC139838
0.785	Intermediate Similarity	NPC221615
0.785	Intermediate Similarity	NPC141191
0.7845	Intermediate Similarity	NPC36754
0.7845	Intermediate Similarity	NPC156252
0.7838	Intermediate Similarity	NPC326994
0.7838	Intermediate Similarity	NPC194620
0.7838	Intermediate Similarity	NPC72813
0.7838	Intermediate Similarity	NPC324327
0.7838	Intermediate Similarity	NPC474421
0.7833	Intermediate Similarity	NPC473709
0.7833	Intermediate Similarity	NPC473919
0.7833	Intermediate Similarity	NPC145238
0.783	Intermediate Similarity	NPC18019
0.783	Intermediate Similarity	NPC24956
0.783	Intermediate Similarity	NPC230800
0.783	Intermediate Similarity	NPC279621
0.783	Intermediate Similarity	NPC476315
0.783	Intermediate Similarity	NPC476009
0.7822	Intermediate Similarity	NPC469483
0.7818	Intermediate Similarity	NPC475676
0.7818	Intermediate Similarity	NPC146731
0.7818	Intermediate Similarity	NPC220964
0.781	Intermediate Similarity	NPC127019
0.7807	Intermediate Similarity	NPC95290
0.7807	Intermediate Similarity	NPC189338
0.7807	Intermediate Similarity	NPC241477
0.7807	Intermediate Similarity	NPC317687
0.7798	Intermediate Similarity	NPC105725
0.7798	Intermediate Similarity	NPC474709
0.7797	Intermediate Similarity	NPC19336
0.7797	Intermediate Similarity	NPC472759
0.7797	Intermediate Similarity	NPC329080
0.7797	Intermediate Similarity	NPC185876
0.7788	Intermediate Similarity	NPC131209
0.7788	Intermediate Similarity	NPC221282
0.7788	Intermediate Similarity	NPC15551
0.7788	Intermediate Similarity	NPC30515
0.7788	Intermediate Similarity	NPC50223
0.7788	Intermediate Similarity	NPC184463
0.7788	Intermediate Similarity	NPC476705
0.7787	Intermediate Similarity	NPC172823
0.7787	Intermediate Similarity	NPC270109
0.7778	Intermediate Similarity	NPC161060
0.7778	Intermediate Similarity	NPC288876
0.7778	Intermediate Similarity	NPC70865
0.7778	Intermediate Similarity	NPC13710
0.7769	Intermediate Similarity	NPC471939
0.7768	Intermediate Similarity	NPC474664
0.7768	Intermediate Similarity	NPC55972
0.7768	Intermediate Similarity	NPC327286
0.7768	Intermediate Similarity	NPC233379
0.7768	Intermediate Similarity	NPC94377
0.7768	Intermediate Similarity	NPC169888
0.7768	Intermediate Similarity	NPC14862

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 NPC477102 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	271
0.1-0.2	2236
0.2-0.3	3628
0.3-0.4	2008
0.4-0.5	708
0.5-0.6	256
0.6-0.7	36
0.7-0.8	5
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
0.9706	High Similarity	NPD6371	Approved
0.8679	High Similarity	NPD7899	Clinical (unspecified phase)
0.7736	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7692	Intermediate Similarity	NPD6698	Approved
0.7692	Intermediate Similarity	NPD46	Approved
0.7596	Intermediate Similarity	NPD1695	Approved
0.7524	Intermediate Similarity	NPD5785	Approved
0.7358	Intermediate Similarity	NPD7838	Discovery
0.7304	Intermediate Similarity	NPD6686	Approved
0.725	Intermediate Similarity	NPD7115	Discovery
0.7156	Intermediate Similarity	NPD5282	Discontinued
0.713	Intermediate Similarity	NPD7983	Approved
0.7087	Intermediate Similarity	NPD5209	Approved
0.7054	Intermediate Similarity	NPD4225	Approved
0.7048	Intermediate Similarity	NPD5363	Approved
0.6935	Remote Similarity	NPD6319	Approved
0.6917	Remote Similarity	NPD6053	Discontinued
0.6899	Remote Similarity	NPD7319	Approved
0.6887	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6827	Remote Similarity	NPD5369	Approved
0.6797	Remote Similarity	NPD7507	Approved
0.6783	Remote Similarity	NPD5344	Discontinued
0.6762	Remote Similarity	NPD4269	Approved
0.6762	Remote Similarity	NPD4270	Approved
0.6754	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.675	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6698	Remote Similarity	NPD5362	Discontinued
0.6694	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD5786	Approved
0.6667	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6639	Remote Similarity	NPD6412	Phase 2
0.6639	Remote Similarity	NPD8297	Approved
0.6609	Remote Similarity	NPD7638	Approved
0.6589	Remote Similarity	NPD7492	Approved
0.6585	Remote Similarity	NPD4632	Approved
0.6574	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6571	Remote Similarity	NPD4252	Approved
0.6557	Remote Similarity	NPD6650	Approved
0.6557	Remote Similarity	NPD6649	Approved
0.6555	Remote Similarity	NPD6008	Approved
0.6552	Remote Similarity	NPD7639	Approved
0.6552	Remote Similarity	NPD6648	Approved
0.6552	Remote Similarity	NPD7640	Approved
0.6542	Remote Similarity	NPD7154	Phase 3
0.6538	Remote Similarity	NPD6616	Approved
0.6535	Remote Similarity	NPD6054	Approved
0.6529	Remote Similarity	NPD6373	Approved
0.6529	Remote Similarity	NPD6372	Approved
0.6522	Remote Similarity	NPD6084	Phase 2
0.6522	Remote Similarity	NPD6083	Phase 2
0.6512	Remote Similarity	NPD7604	Phase 2
0.6512	Remote Similarity	NPD7642	Approved
0.6508	Remote Similarity	NPD7327	Approved
0.6508	Remote Similarity	NPD7328	Approved
0.65	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6491	Remote Similarity	NPD5695	Phase 3
0.6489	Remote Similarity	NPD7078	Approved
0.6484	Remote Similarity	NPD8513	Phase 3
0.6484	Remote Similarity	NPD7503	Approved
0.6484	Remote Similarity	NPD8517	Approved
0.6484	Remote Similarity	NPD8515	Approved
0.6484	Remote Similarity	NPD8033	Approved
0.6484	Remote Similarity	NPD8516	Approved
0.6466	Remote Similarity	NPD5696	Approved
0.646	Remote Similarity	NPD5778	Approved
0.646	Remote Similarity	NPD5779	Approved
0.646	Remote Similarity	NPD6399	Phase 3
0.6457	Remote Similarity	NPD7516	Approved
0.6455	Remote Similarity	NPD4251	Approved
0.6455	Remote Similarity	NPD4250	Approved
0.6449	Remote Similarity	NPD6435	Approved
0.6449	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6446	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6446	Remote Similarity	NPD6881	Approved
0.6446	Remote Similarity	NPD6899	Approved
0.6439	Remote Similarity	NPD7736	Approved
0.6434	Remote Similarity	NPD6370	Approved
0.6422	Remote Similarity	NPD1694	Approved
0.6417	Remote Similarity	NPD5739	Approved
0.6417	Remote Similarity	NPD6675	Approved
0.6417	Remote Similarity	NPD6402	Approved
0.6417	Remote Similarity	NPD7128	Approved
0.6415	Remote Similarity	NPD4820	Approved
0.6415	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6415	Remote Similarity	NPD4819	Approved
0.6415	Remote Similarity	NPD4821	Approved
0.6415	Remote Similarity	NPD4822	Approved
0.6412	Remote Similarity	NPD8273	Phase 1
0.6406	Remote Similarity	NPD6059	Approved
0.6406	Remote Similarity	NPD8294	Approved
0.6406	Remote Similarity	NPD8377	Approved
0.6381	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6372	Remote Similarity	NPD7637	Suspended
0.6371	Remote Similarity	NPD6882	Approved
0.6364	Remote Similarity	NPD4249	Approved
0.6364	Remote Similarity	NPD5697	Approved
0.6364	Remote Similarity	NPD8293	Discontinued
0.6357	Remote Similarity	NPD8378	Approved
0.6357	Remote Similarity	NPD6015	Approved
0.6357	Remote Similarity	NPD8296	Approved
0.6357	Remote Similarity	NPD8380	Approved
0.6357	Remote Similarity	NPD8335	Approved
0.6357	Remote Similarity	NPD8379	Approved
0.6357	Remote Similarity	NPD6016	Approved
0.6348	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6341	Remote Similarity	NPD7290	Approved
0.6341	Remote Similarity	NPD7102	Approved
0.6341	Remote Similarity	NPD6883	Approved
0.6341	Remote Similarity	NPD4634	Approved
0.632	Remote Similarity	NPD8133	Approved
0.6311	Remote Similarity	NPD7320	Approved
0.6308	Remote Similarity	NPD5988	Approved
0.6299	Remote Similarity	NPD6009	Approved
0.6296	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6296	Remote Similarity	NPD7260	Phase 2
0.629	Remote Similarity	NPD8130	Phase 1
0.629	Remote Similarity	NPD6847	Approved
0.629	Remote Similarity	NPD6617	Approved
0.629	Remote Similarity	NPD6869	Approved
0.6262	Remote Similarity	NPD5368	Approved
0.626	Remote Similarity	NPD6012	Approved
0.626	Remote Similarity	NPD7829	Approved
0.626	Remote Similarity	NPD8328	Phase 3
0.626	Remote Similarity	NPD6014	Approved
0.626	Remote Similarity	NPD7830	Approved
0.626	Remote Similarity	NPD6013	Approved
0.6241	Remote Similarity	NPD8074	Phase 3
0.6231	Remote Similarity	NPD5983	Phase 2
0.623	Remote Similarity	NPD5701	Approved
0.6228	Remote Similarity	NPD5693	Phase 1
0.6228	Remote Similarity	NPD5281	Approved
0.6228	Remote Similarity	NPD5284	Approved
0.6228	Remote Similarity	NPD6411	Approved
0.6226	Remote Similarity	NPD4268	Approved
0.6226	Remote Similarity	NPD4271	Approved
0.6216	Remote Similarity	NPD7334	Approved
0.6216	Remote Similarity	NPD6684	Approved
0.6216	Remote Similarity	NPD5330	Approved
0.6216	Remote Similarity	NPD7146	Approved
0.6216	Remote Similarity	NPD6409	Approved
0.6216	Remote Similarity	NPD7521	Approved
0.6187	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6179	Remote Similarity	NPD6011	Approved
0.6165	Remote Similarity	NPD6336	Discontinued
0.6154	Remote Similarity	NPD7839	Suspended
0.6106	Remote Similarity	NPD6903	Approved
0.6106	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6102	Remote Similarity	NPD7902	Approved
0.6091	Remote Similarity	NPD5332	Approved
0.6091	Remote Similarity	NPD5331	Approved
0.6068	Remote Similarity	NPD4629	Approved
0.6068	Remote Similarity	NPD5210	Approved
0.6055	Remote Similarity	NPD4790	Discontinued
0.6053	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6053	Remote Similarity	NPD6673	Approved
0.6053	Remote Similarity	NPD6904	Approved
0.6053	Remote Similarity	NPD6080	Approved
0.6053	Remote Similarity	NPD4753	Phase 2
0.6053	Remote Similarity	NPD6101	Approved
0.6047	Remote Similarity	NPD7500	Approved
0.6045	Remote Similarity	NPD8451	Approved
0.6033	Remote Similarity	NPD7632	Discontinued
0.6033	Remote Similarity	NPD5211	Phase 2
0.6032	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6018	Remote Similarity	NPD7524	Approved
0.6014	Remote Similarity	NPD6845	Suspended
0.6	Remote Similarity	NPD8448	Approved
0.6	Remote Similarity	NPD5285	Approved
0.6	Remote Similarity	NPD5286	Approved
0.6	Remote Similarity	NPD4696	Approved
0.6	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6	Remote Similarity	NPD7641	Discontinued
0.5985	Remote Similarity	NPD5956	Approved
0.5985	Remote Similarity	NPD8444	Approved
0.5985	Remote Similarity	NPD6921	Approved
0.5983	Remote Similarity	NPD7748	Approved
0.5983	Remote Similarity	NPD6001	Approved
0.5969	Remote Similarity	NPD6274	Approved
0.5966	Remote Similarity	NPD4755	Approved
0.5965	Remote Similarity	NPD5737	Approved
0.5965	Remote Similarity	NPD6672	Approved
0.5956	Remote Similarity	NPD6033	Approved
0.5954	Remote Similarity	NPD7101	Approved
0.5954	Remote Similarity	NPD4522	Approved
0.5954	Remote Similarity	NPD7100	Approved
0.5948	Remote Similarity	NPD6050	Approved
0.5946	Remote Similarity	NPD6110	Phase 1
0.5935	Remote Similarity	NPD5141	Approved
0.5929	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.5923	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.5913	Remote Similarity	NPD6051	Approved
0.5913	Remote Similarity	NPD5370	Suspended
0.5902	Remote Similarity	NPD4633	Approved
0.5902	Remote Similarity	NPD5224	Approved
0.5902	Remote Similarity	NPD5225	Approved
0.5902	Remote Similarity	NPD5226	Approved
0.5897	Remote Similarity	NPD4202	Approved
0.5893	Remote Similarity	NPD3666	Approved
0.5893	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.5893	Remote Similarity	NPD6400	Clinical (unspecified phase)

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