NPASS Compound

Structure

NPC473488 OpenBabel07101719252D 41 44 0 0 1 0 0 0 0 0999 V2000 9.7707 -7.8087 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1486 0.3732 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1974 -0.4511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7551 -2.0903 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3786 -1.3085 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7792 -7.9392 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1705 -7.1459 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1790 -7.2764 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5703 -6.4830 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5788 -6.6135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9701 -5.8202 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9786 -5.9507 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3699 -5.1574 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3784 -5.2879 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7696 -4.4945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7782 -4.6251 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1694 -3.8317 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8220 -3.9622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4308 -3.1689 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4010 -1.0104 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8019 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7099 0.9770 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1486 0.3732 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2225 -0.2285 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8019 0.7464 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4010 -1.0104 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2742 -0.5278 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0481 -2.2450 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0245 -0.2285 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7099 -0.2306 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9010 1.1803 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5278 -0.5278 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3898 -1.1594 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 0.7464 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 -0.0566 -2.1145 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0189 -1.1817 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9010 2.1803 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1451 -1.4517 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9978 0.0660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6568 -1.4517 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 2 23 1 0 0 0 0 3 24 1 0 0 0 0 4 33 1 0 0 0 0 5 33 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 8 9 1 0 0 0 0 9 10 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 28 1 0 0 0 0 20 24 1 0 0 0 0 21 27 2 0 0 0 0 22 23 2 0 0 0 0 22 34 1 0 0 0 0 23 30 1 0 0 0 0 24 34 1 6 0 0 0 25 21 1 6 0 0 0 25 29 1 0 0 0 0 25 31 1 0 0 0 0 26 20 1 1 0 0 0 26 29 1 0 0 0 0 26 33 1 0 0 0 0 27 32 1 0 0 0 0 27 41 1 0 0 0 0 28 36 2 0 0 0 0 28 41 1 0 0 0 0 29 33 1 1 0 0 0 30 35 1 6 0 0 0 30 37 1 0 0 0 0 31 34 1 0 0 0 0 31 38 2 0 0 0 0 32 35 1 6 0 0 0 32 39 1 0 0 0 0 34 35 1 1 0 0 0 35 40 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	572.41
Volume:	621.886
LogP:	8.391
LogD:	5.482
LogS:	-4.094
# Rotatable Bonds:	16
TPSA:	104.06
# H-Bond Aceptor:	6
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.113
Synthetic Accessibility Score:	6.003
Fsp3:	0.829
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.993
MDCK Permeability:	1.6398844309151173e-05
Pgp-inhibitor:	0.355
Pgp-substrate:	0.979
Human Intestinal Absorption (HIA):	0.043
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.428
Plasma Protein Binding (PPB):	96.82917022705078%
Volume Distribution (VD):	0.829
Pgp-substrate:	1.81802237033844%

ADMET: Metabolism

CYP1A2-inhibitor:	0.05
CYP1A2-substrate:	0.13
CYP2C19-inhibitor:	0.588
CYP2C19-substrate:	0.818
CYP2C9-inhibitor:	0.45
CYP2C9-substrate:	0.857
CYP2D6-inhibitor:	0.017
CYP2D6-substrate:	0.018
CYP3A4-inhibitor:	0.76
CYP3A4-substrate:	0.139

ADMET: Excretion

Clearance (CL):	9.3
Half-life (T1/2):	0.051

ADMET: Toxicity

hERG Blockers:	0.887
Human Hepatotoxicity (H-HT):	0.168
Drug-inuced Liver Injury (DILI):	0.124
AMES Toxicity:	0.017
Rat Oral Acute Toxicity:	0.995
Maximum Recommended Daily Dose:	0.999
Skin Sensitization:	0.927
Carcinogencity:	0.124
Eye Corrosion:	0.937
Eye Irritation:	0.598
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: NPC473488

Natural Product ID:	NPC473488
*Common Name:**	KPQZTVYTLWHCAU-JHLCMTBYSA-N
IUPAC Name:	n.a.
Synonyms:	Ingenol 20-Hexadecanoate
Standard InCHIKey:	KPQZTVYTLWHCAU-JHLCMTBYSA-N
Standard InCHI:	InChI=1S/C35H56O6/c1-6-7-8-9-10-11-12-13-14-15-16-17-18-19-28(36)41-27-21-25-29-26(33(29,4)5)20-24(3)34(31(25)38)22-23(2)30(37)35(34,40)32(27)39/h21-22,24-26,29-30,32,37,39-40H,6-20H2,1-5H3/t24-,25+,26-,29+,30+,32-,34+,35-/m1/s1
SMILES:	CCCCCCCCCCCCCCCC(=O)OC1=C[C@H]2[C@H]3[C@H](C3(C)C)C[C@H]([C@]3([C@@]([C@@H]1O)(O)[C@@H](O)C(=C3)C)C2=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL443348
PubChem CID:	44566860
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
NPO15892	Euphorbia quinquecostata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12350147]
NPO15892	Euphorbia quinquecostata	Species	Euphorbiaceae	Eukaryota	stem wood	n.a.	n.a.	PMID[8946746]
NPO15892	Euphorbia quinquecostata	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

Activity Type	# Activity
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified		IC50	=	5300.0	nM	PMID[491409]

☑ 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 NPC473488 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	251
0.1-0.2	1526
0.2-0.3	5256
0.3-0.4	12067
0.4-0.5	12781
0.5-0.6	7567
0.6-0.7	2907
0.7-0.8	307
0.8-0.85	2
0.85-0.9	19
0.9-0.95	12
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC475661
0.95	High Similarity	NPC473911
0.9216	High Similarity	NPC308191
0.9135	High Similarity	NPC287311
0.902	High Similarity	NPC179891
0.8857	High Similarity	NPC257240
0.8762	High Similarity	NPC47951
0.8704	High Similarity	NPC67290
0.8704	High Similarity	NPC133677
0.8704	High Similarity	NPC138303
0.8692	High Similarity	NPC138757
0.8687	High Similarity	NPC261341
0.8679	High Similarity	NPC477103
0.8611	High Similarity	NPC46269
0.8611	High Similarity	NPC106395
0.8585	High Similarity	NPC477102
0.8519	High Similarity	NPC123855
0.8519	High Similarity	NPC76550
0.785	Intermediate Similarity	NPC118405
0.7759	Intermediate Similarity	NPC477092
0.7757	Intermediate Similarity	NPC477950
0.7736	Intermediate Similarity	NPC141191
0.7719	Intermediate Similarity	NPC472400
0.7712	Intermediate Similarity	NPC19464
0.7706	Intermediate Similarity	NPC100487
0.7706	Intermediate Similarity	NPC203659
0.7692	Intermediate Similarity	NPC65829
0.7672	Intermediate Similarity	NPC475401
0.7658	Intermediate Similarity	NPC117604
0.7642	Intermediate Similarity	NPC169205
0.7636	Intermediate Similarity	NPC243998
0.7632	Intermediate Similarity	NPC472757
0.7627	Intermediate Similarity	NPC472401
0.7619	Intermediate Similarity	NPC472469
0.7615	Intermediate Similarity	NPC110989
0.7607	Intermediate Similarity	NPC275696
0.7607	Intermediate Similarity	NPC5991
0.7607	Intermediate Similarity	NPC22628
0.7607	Intermediate Similarity	NPC471108
0.7607	Intermediate Similarity	NPC5989
0.7607	Intermediate Similarity	NPC255081
0.7586	Intermediate Similarity	NPC10721
0.7586	Intermediate Similarity	NPC475305
0.7586	Intermediate Similarity	NPC156252
0.7568	Intermediate Similarity	NPC26617
0.7551	Intermediate Similarity	NPC470241
0.7547	Intermediate Similarity	NPC185553
0.7545	Intermediate Similarity	NPC309190
0.7524	Intermediate Similarity	NPC167219
0.7523	Intermediate Similarity	NPC225353
0.7521	Intermediate Similarity	NPC472397
0.7521	Intermediate Similarity	NPC471125
0.7521	Intermediate Similarity	NPC146280
0.7521	Intermediate Similarity	NPC124676
0.7521	Intermediate Similarity	NPC472758
0.7521	Intermediate Similarity	NPC171905
0.75	Intermediate Similarity	NPC476705
0.75	Intermediate Similarity	NPC472399
0.75	Intermediate Similarity	NPC471127
0.75	Intermediate Similarity	NPC234858
0.75	Intermediate Similarity	NPC154363
0.7479	Intermediate Similarity	NPC52839
0.7477	Intermediate Similarity	NPC477949
0.7477	Intermediate Similarity	NPC87090
0.7477	Intermediate Similarity	NPC469432
0.7477	Intermediate Similarity	NPC223450
0.7476	Intermediate Similarity	NPC170775
0.7456	Intermediate Similarity	NPC158523
0.7456	Intermediate Similarity	NPC475937
0.7455	Intermediate Similarity	NPC475945
0.7455	Intermediate Similarity	NPC472755
0.7455	Intermediate Similarity	NPC475871
0.7453	Intermediate Similarity	NPC90121
0.7453	Intermediate Similarity	NPC48803
0.7453	Intermediate Similarity	NPC275960
0.7453	Intermediate Similarity	NPC193645
0.7451	Intermediate Similarity	NPC237540
0.7434	Intermediate Similarity	NPC15218
0.7431	Intermediate Similarity	NPC477356
0.7431	Intermediate Similarity	NPC472753
0.7417	Intermediate Similarity	NPC162009
0.7417	Intermediate Similarity	NPC257017
0.7407	Intermediate Similarity	NPC477355
0.7404	Intermediate Similarity	NPC469368
0.7404	Intermediate Similarity	NPC145666
0.7398	Intermediate Similarity	NPC236999
0.7395	Intermediate Similarity	NPC145182
0.7395	Intermediate Similarity	NPC471128
0.7395	Intermediate Similarity	NPC157252
0.7395	Intermediate Similarity	NPC475885
0.7395	Intermediate Similarity	NPC472759
0.7395	Intermediate Similarity	NPC471126
0.7395	Intermediate Similarity	NPC329080
0.7387	Intermediate Similarity	NPC475676
0.7387	Intermediate Similarity	NPC472756
0.7387	Intermediate Similarity	NPC220964
0.7387	Intermediate Similarity	NPC474741
0.7368	Intermediate Similarity	NPC153036
0.7364	Intermediate Similarity	NPC474747
0.7364	Intermediate Similarity	NPC472754
0.7364	Intermediate Similarity	NPC473928
0.7364	Intermediate Similarity	NPC86077
0.7364	Intermediate Similarity	NPC474709
0.7358	Intermediate Similarity	NPC53685
0.7345	Intermediate Similarity	NPC14862
0.7345	Intermediate Similarity	NPC233379
0.7345	Intermediate Similarity	NPC327286
0.7345	Intermediate Similarity	NPC169888
0.7345	Intermediate Similarity	NPC474664
0.7345	Intermediate Similarity	NPC55972
0.7339	Intermediate Similarity	NPC474718
0.7339	Intermediate Similarity	NPC477521
0.7333	Intermediate Similarity	NPC475972
0.7328	Intermediate Similarity	NPC71889
0.7321	Intermediate Similarity	NPC60315
0.7311	Intermediate Similarity	NPC156745
0.7311	Intermediate Similarity	NPC61520
0.7311	Intermediate Similarity	NPC236918
0.7308	Intermediate Similarity	NPC117405
0.7308	Intermediate Similarity	NPC52198
0.7304	Intermediate Similarity	NPC470961
0.73	Intermediate Similarity	NPC7414
0.73	Intermediate Similarity	NPC89555
0.7297	Intermediate Similarity	NPC474165
0.7297	Intermediate Similarity	NPC475334
0.7297	Intermediate Similarity	NPC475623
0.7297	Intermediate Similarity	NPC69171
0.7297	Intermediate Similarity	NPC473694
0.7297	Intermediate Similarity	NPC4620
0.7295	Intermediate Similarity	NPC473709
0.7295	Intermediate Similarity	NPC145238
0.7295	Intermediate Similarity	NPC473919
0.729	Intermediate Similarity	NPC270013
0.729	Intermediate Similarity	NPC469873
0.729	Intermediate Similarity	NPC36954
0.729	Intermediate Similarity	NPC14961
0.7288	Intermediate Similarity	NPC153651
0.7282	Intermediate Similarity	NPC179659
0.7282	Intermediate Similarity	NPC472007
0.7281	Intermediate Similarity	NPC273433
0.7273	Intermediate Similarity	NPC471401
0.7273	Intermediate Similarity	NPC133907
0.7273	Intermediate Similarity	NPC150923
0.7273	Intermediate Similarity	NPC171759
0.7273	Intermediate Similarity	NPC110443
0.7273	Intermediate Similarity	NPC185141
0.7273	Intermediate Similarity	NPC46998
0.7273	Intermediate Similarity	NPC128733
0.7273	Intermediate Similarity	NPC474742
0.7265	Intermediate Similarity	NPC474872
0.7264	Intermediate Similarity	NPC125180
0.7264	Intermediate Similarity	NPC475912
0.7264	Intermediate Similarity	NPC469692
0.7264	Intermediate Similarity	NPC475788
0.7264	Intermediate Similarity	NPC469645
0.7257	Intermediate Similarity	NPC474421
0.7257	Intermediate Similarity	NPC326994
0.7257	Intermediate Similarity	NPC72813
0.7257	Intermediate Similarity	NPC324327
0.7257	Intermediate Similarity	NPC194620
0.7255	Intermediate Similarity	NPC165162
0.725	Intermediate Similarity	NPC185876
0.725	Intermediate Similarity	NPC474370
0.725	Intermediate Similarity	NPC19336
0.7241	Intermediate Similarity	NPC191620
0.7241	Intermediate Similarity	NPC473522
0.7241	Intermediate Similarity	NPC215643
0.7241	Intermediate Similarity	NPC221511
0.7241	Intermediate Similarity	NPC170212
0.7241	Intermediate Similarity	NPC89227
0.7241	Intermediate Similarity	NPC475277
0.7241	Intermediate Similarity	NPC477093
0.7241	Intermediate Similarity	NPC17138
0.7241	Intermediate Similarity	NPC265499
0.7241	Intermediate Similarity	NPC151216
0.7241	Intermediate Similarity	NPC101825
0.7238	Intermediate Similarity	NPC313670
0.7238	Intermediate Similarity	NPC166554
0.7238	Intermediate Similarity	NPC129419
0.7232	Intermediate Similarity	NPC470104
0.7232	Intermediate Similarity	NPC121518
0.7232	Intermediate Similarity	NPC475331
0.7232	Intermediate Similarity	NPC103298
0.7232	Intermediate Similarity	NPC80809
0.7232	Intermediate Similarity	NPC201144
0.7232	Intermediate Similarity	NPC181104
0.7232	Intermediate Similarity	NPC475335
0.7232	Intermediate Similarity	NPC288502
0.7227	Intermediate Similarity	NPC288679
0.7227	Intermediate Similarity	NPC472760
0.7227	Intermediate Similarity	NPC161060
0.7227	Intermediate Similarity	NPC329736
0.7227	Intermediate Similarity	NPC186525
0.7222	Intermediate Similarity	NPC135576
0.7222	Intermediate Similarity	NPC93271
0.7222	Intermediate Similarity	NPC476315
0.7217	Intermediate Similarity	NPC29133
0.7217	Intermediate Similarity	NPC161816
0.7217	Intermediate Similarity	NPC115257
0.7213	Intermediate Similarity	NPC473802

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 NPC473488 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	250
0.1-0.2	2214
0.2-0.3	3712
0.3-0.4	2033
0.4-0.5	660
0.5-0.6	238
0.6-0.7	38
0.7-0.8	4
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8857	High Similarity	NPD6371	Approved
0.7568	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.7453	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.74	Intermediate Similarity	NPD7154	Phase 3
0.7353	Intermediate Similarity	NPD5786	Approved
0.7333	Intermediate Similarity	NPD7983	Approved
0.73	Intermediate Similarity	NPD4270	Approved
0.73	Intermediate Similarity	NPD4269	Approved
0.7238	Intermediate Similarity	NPD5785	Approved
0.7228	Intermediate Similarity	NPD5362	Discontinued
0.72	Intermediate Similarity	NPD5369	Approved
0.71	Intermediate Similarity	NPD4252	Approved
0.7087	Intermediate Similarity	NPD5363	Approved
0.7	Intermediate Similarity	NPD7115	Discovery
0.6961	Remote Similarity	NPD6435	Approved
0.6931	Remote Similarity	NPD4822	Approved
0.6931	Remote Similarity	NPD4821	Approved
0.6931	Remote Similarity	NPD4820	Approved
0.6931	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6931	Remote Similarity	NPD4819	Approved
0.69	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6881	Remote Similarity	NPD5282	Discontinued
0.6792	Remote Similarity	NPD4250	Approved
0.6792	Remote Similarity	NPD4251	Approved
0.6789	Remote Similarity	NPD5779	Approved
0.6789	Remote Similarity	NPD5778	Approved
0.6786	Remote Similarity	NPD4225	Approved
0.6765	Remote Similarity	NPD5368	Approved
0.6759	Remote Similarity	NPD46	Approved
0.6759	Remote Similarity	NPD6698	Approved
0.6733	Remote Similarity	NPD4268	Approved
0.6733	Remote Similarity	NPD4271	Approved
0.6698	Remote Similarity	NPD4249	Approved
0.6697	Remote Similarity	NPD6411	Approved
0.6667	Remote Similarity	NPD1695	Approved
0.6667	Remote Similarity	NPD8297	Approved
0.6667	Remote Similarity	NPD6053	Discontinued
0.6636	Remote Similarity	NPD6399	Phase 3
0.6604	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6581	Remote Similarity	NPD6675	Approved
0.6581	Remote Similarity	NPD7128	Approved
0.6581	Remote Similarity	NPD6402	Approved
0.6581	Remote Similarity	NPD5739	Approved
0.6571	Remote Similarity	NPD5331	Approved
0.6571	Remote Similarity	NPD5332	Approved
0.6555	Remote Similarity	NPD6373	Approved
0.6555	Remote Similarity	NPD6372	Approved
0.6549	Remote Similarity	NPD6083	Phase 2
0.6549	Remote Similarity	NPD6084	Phase 2
0.6545	Remote Similarity	NPD7637	Suspended
0.6538	Remote Similarity	NPD4790	Discontinued
0.6514	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6514	Remote Similarity	NPD6101	Approved
0.6476	Remote Similarity	NPD5209	Approved
0.6476	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD6899	Approved
0.6471	Remote Similarity	NPD7320	Approved
0.6471	Remote Similarity	NPD6881	Approved
0.646	Remote Similarity	NPD7839	Suspended
0.6455	Remote Similarity	NPD7838	Discovery
0.6446	Remote Similarity	NPD6649	Approved
0.6446	Remote Similarity	NPD6650	Approved
0.6446	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6446	Remote Similarity	NPD8130	Phase 1
0.6429	Remote Similarity	NPD6319	Approved
0.6387	Remote Similarity	NPD5701	Approved
0.6387	Remote Similarity	NPD5697	Approved
0.6378	Remote Similarity	NPD8513	Phase 3
0.6378	Remote Similarity	NPD8517	Approved
0.6378	Remote Similarity	NPD8515	Approved
0.6378	Remote Similarity	NPD8516	Approved
0.6372	Remote Similarity	NPD5695	Phase 3
0.6364	Remote Similarity	NPD7102	Approved
0.6364	Remote Similarity	NPD7290	Approved
0.6364	Remote Similarity	NPD6883	Approved
0.6364	Remote Similarity	NPD5370	Suspended
0.6348	Remote Similarity	NPD5696	Approved
0.6333	Remote Similarity	NPD6686	Approved
0.6311	Remote Similarity	NPD6617	Approved
0.6311	Remote Similarity	NPD6847	Approved
0.6311	Remote Similarity	NPD6869	Approved
0.6288	Remote Similarity	NPD7319	Approved
0.6281	Remote Similarity	NPD6014	Approved
0.6281	Remote Similarity	NPD6012	Approved
0.6281	Remote Similarity	NPD6013	Approved
0.626	Remote Similarity	NPD6882	Approved
0.626	Remote Similarity	NPD8293	Discontinued
0.625	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.625	Remote Similarity	NPD6412	Phase 2
0.6231	Remote Similarity	NPD7492	Approved
0.6228	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6212	Remote Similarity	NPD7736	Approved
0.621	Remote Similarity	NPD4632	Approved
0.6198	Remote Similarity	NPD6011	Approved
0.6198	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6186	Remote Similarity	NPD5211	Phase 2
0.6183	Remote Similarity	NPD8273	Phase 1
0.6183	Remote Similarity	NPD7507	Approved
0.6183	Remote Similarity	NPD6616	Approved
0.6182	Remote Similarity	NPD7524	Approved
0.6179	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6172	Remote Similarity	NPD6059	Approved
0.6172	Remote Similarity	NPD6054	Approved
0.6167	Remote Similarity	NPD6008	Approved
0.6154	Remote Similarity	NPD7604	Phase 2
0.6147	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6136	Remote Similarity	NPD7078	Approved
0.6136	Remote Similarity	NPD8074	Phase 3
0.6121	Remote Similarity	NPD4755	Approved
0.6121	Remote Similarity	NPD7902	Approved
0.6111	Remote Similarity	NPD6110	Phase 1
0.6106	Remote Similarity	NPD5281	Approved
0.6106	Remote Similarity	NPD5284	Approved
0.6102	Remote Similarity	NPD5344	Discontinued
0.6098	Remote Similarity	NPD4634	Approved
0.6091	Remote Similarity	NPD7521	Approved
0.6091	Remote Similarity	NPD7334	Approved
0.6091	Remote Similarity	NPD6409	Approved
0.6091	Remote Similarity	NPD5330	Approved
0.6091	Remote Similarity	NPD7146	Approved
0.6091	Remote Similarity	NPD6684	Approved
0.6083	Remote Similarity	NPD5141	Approved
0.6077	Remote Similarity	NPD6370	Approved
0.6071	Remote Similarity	NPD4753	Phase 2
0.6068	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6055	Remote Similarity	NPD4786	Approved
0.6055	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6031	Remote Similarity	NPD8328	Phase 3
0.6017	Remote Similarity	NPD7639	Approved
0.6017	Remote Similarity	NPD4700	Approved
0.6017	Remote Similarity	NPD5285	Approved
0.6017	Remote Similarity	NPD7640	Approved
0.6017	Remote Similarity	NPD4696	Approved
0.6017	Remote Similarity	NPD5286	Approved
0.6016	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6	Remote Similarity	NPD6016	Approved
0.6	Remote Similarity	NPD6015	Approved
0.6	Remote Similarity	NPD7748	Approved
0.5985	Remote Similarity	NPD8341	Approved
0.5985	Remote Similarity	NPD8340	Approved
0.5985	Remote Similarity	NPD8299	Approved
0.5985	Remote Similarity	NPD8342	Approved
0.5984	Remote Similarity	NPD6274	Approved
0.5982	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.5982	Remote Similarity	NPD6903	Approved
0.5969	Remote Similarity	NPD7101	Approved
0.5969	Remote Similarity	NPD7100	Approved
0.5965	Remote Similarity	NPD8034	Phase 2
0.5965	Remote Similarity	NPD8035	Phase 2
0.5963	Remote Similarity	NPD6695	Phase 3
0.5954	Remote Similarity	NPD5988	Approved
0.5952	Remote Similarity	NPD8133	Approved
0.5948	Remote Similarity	NPD5210	Approved
0.5948	Remote Similarity	NPD4629	Approved
0.5946	Remote Similarity	NPD6098	Approved
0.5938	Remote Similarity	NPD6009	Approved
0.5938	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.5938	Remote Similarity	NPD8137	Clinical (unspecified phase)
0.5932	Remote Similarity	NPD7638	Approved
0.5929	Remote Similarity	NPD6673	Approved
0.5929	Remote Similarity	NPD6904	Approved
0.5929	Remote Similarity	NPD6080	Approved
0.5917	Remote Similarity	NPD5226	Approved
0.5917	Remote Similarity	NPD4633	Approved
0.5917	Remote Similarity	NPD5224	Approved
0.5917	Remote Similarity	NPD5225	Approved
0.5913	Remote Similarity	NPD4202	Approved
0.5909	Remote Similarity	NPD3666	Approved
0.5909	Remote Similarity	NPD3133	Approved
0.5909	Remote Similarity	NPD3665	Phase 1
0.5893	Remote Similarity	NPD7750	Discontinued
0.5891	Remote Similarity	NPD6335	Approved
0.5887	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.5878	Remote Similarity	NPD6908	Approved
0.5878	Remote Similarity	NPD5983	Phase 2
0.5878	Remote Similarity	NPD7503	Approved
0.5878	Remote Similarity	NPD6909	Approved
0.5878	Remote Similarity	NPD8274	Clinical (unspecified phase)
0.5878	Remote Similarity	NPD8033	Approved
0.5872	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.5872	Remote Similarity	NPD3667	Approved
0.5868	Remote Similarity	NPD5175	Approved
0.5868	Remote Similarity	NPD5174	Approved
0.5862	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.5862	Remote Similarity	NPD7900	Approved
0.5862	Remote Similarity	NPD6001	Approved
0.5856	Remote Similarity	NPD1694	Approved
0.5856	Remote Similarity	NPD1696	Phase 3
0.5841	Remote Similarity	NPD5737	Approved
0.5841	Remote Similarity	NPD6672	Approved
0.584	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.5833	Remote Similarity	NPD8080	Discontinued
0.5833	Remote Similarity	NPD5223	Approved
0.5826	Remote Similarity	NPD5693	Phase 1
0.5826	Remote Similarity	NPD6050	Approved
0.5826	Remote Similarity	NPD7515	Phase 2
0.5821	Remote Similarity	NPD8451	Approved
0.5821	Remote Similarity	NPD6336	Discontinued
0.5818	Remote Similarity	NPD4788	Approved
0.5814	Remote Similarity	NPD6317	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