NPASS Compound

Structure

NPC46413 OpenBabel07101718282D 34 37 0 0 1 0 0 0 0 0999 V2000 4.5767 -5.5064 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9631 1.9445 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7138 -4.4271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4048 -3.4761 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4593 -1.4135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4538 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.9563 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7431 1.2872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5277 -5.1973 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2272 -1.7330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5362 -2.6840 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8745 -1.1977 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5873 -0.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9631 -2.0555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9631 0.9445 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8963 -0.9898 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1835 -2.1488 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0970 -2.5555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5144 -2.8920 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9631 -1.0555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6092 0.1691 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.9925 -3.5501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0970 0.4445 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8291 -0.5555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7357 -4.2192 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 0.2079 0.9781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8291 0.4445 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.0144 -3.7580 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.0970 -0.5555 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.2310 0.9445 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6951 -1.0555 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2024 1.0827 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 9 2 0 0 0 0 3 25 1 0 0 0 0 4 25 1 0 0 0 0 5 26 1 0 0 0 0 6 26 1 0 0 0 0 7 27 1 0 0 0 0 8 27 1 0 0 0 0 9 25 1 0 0 0 0 10 11 2 0 0 0 0 10 16 1 0 0 0 0 11 19 1 0 0 0 0 12 16 2 0 0 0 0 12 17 1 0 0 0 0 13 16 1 0 0 0 0 14 18 1 0 0 0 0 14 20 2 0 0 0 0 15 2 1 6 0 0 0 15 23 1 0 0 0 0 15 28 1 0 0 0 0 17 18 1 0 0 0 0 17 19 2 0 0 0 0 18 22 2 0 0 0 0 19 29 1 0 0 0 0 20 24 1 0 0 0 0 20 30 1 0 0 0 0 21 13 1 6 0 0 0 21 26 1 0 0 0 0 21 33 1 0 0 0 0 22 25 1 0 0 0 0 22 29 1 0 0 0 0 23 30 2 0 0 0 0 23 31 1 0 0 0 0 24 28 2 0 0 0 0 24 32 1 0 0 0 0 26 34 1 0 0 0 0 27 33 1 0 0 0 0 27 34 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	465.26
Volume:	488.382
LogP:	4.803
LogD:	3.29
LogS:	-3.673
# Rotatable Bonds:	6
TPSA:	100.23
# H-Bond Aceptor:	7
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.455
Synthetic Accessibility Score:	4.127
Fsp3:	0.481
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:	-5.059
MDCK Permeability:	1.8884329620050266e-05
Pgp-inhibitor:	0.99
Pgp-substrate:	0.005
Human Intestinal Absorption (HIA):	0.242
20% Bioavailability (F20%):	0.776
30% Bioavailability (F30%):	0.279

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.14
Plasma Protein Binding (PPB):	98.73772430419922%
Volume Distribution (VD):	0.544
Pgp-substrate:	1.54401433467865%

ADMET: Metabolism

CYP1A2-inhibitor:	0.041
CYP1A2-substrate:	0.448
CYP2C19-inhibitor:	0.419
CYP2C19-substrate:	0.338
CYP2C9-inhibitor:	0.843
CYP2C9-substrate:	0.903
CYP2D6-inhibitor:	0.375
CYP2D6-substrate:	0.569
CYP3A4-inhibitor:	0.795
CYP3A4-substrate:	0.885

ADMET: Excretion

Clearance (CL):	4.119
Half-life (T1/2):	0.66

ADMET: Toxicity

hERG Blockers:	0.04
Human Hepatotoxicity (H-HT):	0.601
Drug-inuced Liver Injury (DILI):	0.984
AMES Toxicity:	0.041
Rat Oral Acute Toxicity:	0.938
Maximum Recommended Daily Dose:	0.441
Skin Sensitization:	0.044
Carcinogencity:	0.81
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.986

Download Data

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

Natural Product: NPC46413

Natural Product ID:	NPC46413
*Common Name:**	Variecolorin D
IUPAC Name:	(3S,6Z)-3-methyl-6-[[2-(2-methylbut-3-en-2-yl)-5-[[(4R)-2,2,5,5-tetramethyl-1,3-dioxolan-4-yl]methyl]-1H-indol-3-yl]methylidene]piperazine-2,5-dione
Synonyms:	Variecolorin D
Standard InCHIKey:	OCPAKGPFBHKSHC-MDROSMRXSA-N
Standard InCHI:	InChI=1S/C27H35N3O4/c1-9-25(3,4)22-18(14-20-24(32)28-15(2)23(31)30-20)17-12-16(10-11-19(17)29-22)13-21-26(5,6)34-27(7,8)33-21/h9-12,14-15,21,29H,1,13H2,2-8H3,(H,28,32)(H,30,31)/b20-14-/t15-,21+/m0/s1
SMILES:	C=CC(c1[nH]c2c(c1/C=C/1N=C(O)[C@@H](N=C1O)C)cc(cc2)C[C@H]1OC(OC1(C)C)(C)C)(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL250875
PubChem CID:	23655528
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino 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
NPO31540	Aspergillus variecolor	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/jo00010a040]
NPO31540	Aspergillus variecolor	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17896816]
NPO31540	Aspergillus variecolor	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17965475]

☑ 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	5

Activity Type	# Activity
Cell Line	3
NON-MOLECULAR	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	IC50	>	50000.0	nM	PMID[458410]
NPT116	Cell Line	HL-60	Homo sapiens	IC50	>	50000.0	nM	PMID[458410]
NPT181	Cell Line	Bel-7402	Homo sapiens	IC50	>	50000.0	nM	PMID[458410]
NPT35	Others	n.a.		IC50	=	88000.0	nM	PMID[458410]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	50000.0	nM	PMID[458410]

☑ 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 NPC46413 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	302
0.1-0.2	1413
0.2-0.3	8206
0.3-0.4	21354
0.4-0.5	6690
0.5-0.6	2931
0.6-0.7	1463
0.7-0.8	314
0.8-0.85	17
0.85-0.9	5
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.929	High Similarity	NPC270009
0.9167	High Similarity	NPC34508
0.9017	High Similarity	NPC472444
0.8851	High Similarity	NPC192270
0.8846	High Similarity	NPC32200
0.8844	High Similarity	NPC472443
0.8671	High Similarity	NPC472586
0.858	High Similarity	NPC473320
0.8571	High Similarity	NPC293472
0.8563	High Similarity	NPC38736
0.8529	High Similarity	NPC16667
0.8514	High Similarity	NPC288785
0.843	Intermediate Similarity	NPC470508
0.8412	Intermediate Similarity	NPC67056
0.8391	Intermediate Similarity	NPC280548
0.8343	Intermediate Similarity	NPC471458
0.8343	Intermediate Similarity	NPC470507
0.8323	Intermediate Similarity	NPC124005
0.8323	Intermediate Similarity	NPC37548
0.8323	Intermediate Similarity	NPC187951
0.8294	Intermediate Similarity	NPC285469
0.8235	Intermediate Similarity	NPC207726
0.8204	Intermediate Similarity	NPC129042
0.8187	Intermediate Similarity	NPC184476
0.8161	Intermediate Similarity	NPC472587
0.8152	Intermediate Similarity	NPC34271
0.8136	Intermediate Similarity	NPC6982
0.8084	Intermediate Similarity	NPC242556
0.7977	Intermediate Similarity	NPC141353
0.7967	Intermediate Similarity	NPC198339
0.7955	Intermediate Similarity	NPC311276
0.7935	Intermediate Similarity	NPC165201
0.788	Intermediate Similarity	NPC19679
0.7853	Intermediate Similarity	NPC271734
0.7842	Intermediate Similarity	NPC133366
0.7833	Intermediate Similarity	NPC470498
0.7821	Intermediate Similarity	NPC154293
0.7807	Intermediate Similarity	NPC119700
0.7789	Intermediate Similarity	NPC474177
0.7765	Intermediate Similarity	NPC49954
0.7765	Intermediate Similarity	NPC474561
0.7761	Intermediate Similarity	NPC97388
0.776	Intermediate Similarity	NPC232130
0.7753	Intermediate Similarity	NPC40779
0.7753	Intermediate Similarity	NPC194640
0.7722	Intermediate Similarity	NPC201700
0.7717	Intermediate Similarity	NPC6093
0.7711	Intermediate Similarity	NPC473547
0.7708	Intermediate Similarity	NPC205403
0.7704	Intermediate Similarity	NPC476115
0.7701	Intermediate Similarity	NPC473189
0.77	Intermediate Similarity	NPC250129
0.7697	Intermediate Similarity	NPC282231
0.7692	Intermediate Similarity	NPC97525
0.7677	Intermediate Similarity	NPC474905
0.7667	Intermediate Similarity	NPC160105
0.7667	Intermediate Similarity	NPC54988
0.7663	Intermediate Similarity	NPC151939
0.7653	Intermediate Similarity	NPC123019
0.7653	Intermediate Similarity	NPC193761
0.765	Intermediate Similarity	NPC475165
0.765	Intermediate Similarity	NPC329688
0.765	Intermediate Similarity	NPC189812
0.764	Intermediate Similarity	NPC279918
0.7638	Intermediate Similarity	NPC314957
0.7632	Intermediate Similarity	NPC206967
0.7627	Intermediate Similarity	NPC299594
0.7627	Intermediate Similarity	NPC469762
0.7624	Intermediate Similarity	NPC63751
0.7619	Intermediate Similarity	NPC317030
0.7617	Intermediate Similarity	NPC231342
0.7606	Intermediate Similarity	NPC476319
0.76	Intermediate Similarity	NPC477548
0.7598	Intermediate Similarity	NPC96131
0.7594	Intermediate Similarity	NPC139291
0.7594	Intermediate Similarity	NPC472108
0.7581	Intermediate Similarity	NPC300688
0.7579	Intermediate Similarity	NPC173028
0.7579	Intermediate Similarity	NPC65215
0.7571	Intermediate Similarity	NPC469785
0.7568	Intermediate Similarity	NPC59269
0.7566	Intermediate Similarity	NPC235684
0.7562	Intermediate Similarity	NPC475422
0.7557	Intermediate Similarity	NPC25008
0.7557	Intermediate Similarity	NPC469765
0.7557	Intermediate Similarity	NPC469763
0.7557	Intermediate Similarity	NPC469786
0.7557	Intermediate Similarity	NPC73952
0.7557	Intermediate Similarity	NPC469760
0.7557	Intermediate Similarity	NPC259644
0.7553	Intermediate Similarity	NPC472294
0.755	Intermediate Similarity	NPC127677
0.754	Intermediate Similarity	NPC302191
0.754	Intermediate Similarity	NPC314394
0.7539	Intermediate Similarity	NPC469470
0.7539	Intermediate Similarity	NPC469501
0.7538	Intermediate Similarity	NPC473747
0.7527	Intermediate Similarity	NPC72980
0.7527	Intermediate Similarity	NPC317430
0.7526	Intermediate Similarity	NPC204565
0.7514	Intermediate Similarity	NPC211572
0.7514	Intermediate Similarity	NPC75540
0.7514	Intermediate Similarity	NPC70922
0.7514	Intermediate Similarity	NPC80597
0.7514	Intermediate Similarity	NPC212376
0.7513	Intermediate Similarity	NPC163421
0.7513	Intermediate Similarity	NPC300183
0.7513	Intermediate Similarity	NPC188387
0.7512	Intermediate Similarity	NPC284102
0.75	Intermediate Similarity	NPC46225
0.75	Intermediate Similarity	NPC282033
0.75	Intermediate Similarity	NPC314603
0.7488	Intermediate Similarity	NPC235900
0.7476	Intermediate Similarity	NPC475424
0.7476	Intermediate Similarity	NPC79107
0.7474	Intermediate Similarity	NPC474707
0.7473	Intermediate Similarity	NPC68354
0.7463	Intermediate Similarity	NPC87755
0.7463	Intermediate Similarity	NPC258062
0.7462	Intermediate Similarity	NPC475151
0.7462	Intermediate Similarity	NPC214428
0.746	Intermediate Similarity	NPC190007
0.7459	Intermediate Similarity	NPC102423
0.7459	Intermediate Similarity	NPC476118
0.745	Intermediate Similarity	NPC187456
0.745	Intermediate Similarity	NPC476106
0.7449	Intermediate Similarity	NPC470499
0.7448	Intermediate Similarity	NPC314333
0.7448	Intermediate Similarity	NPC95783
0.7446	Intermediate Similarity	NPC158129
0.7444	Intermediate Similarity	NPC131718
0.7443	Intermediate Similarity	NPC105818
0.7443	Intermediate Similarity	NPC24678
0.7437	Intermediate Similarity	NPC477135
0.7437	Intermediate Similarity	NPC98715
0.7433	Intermediate Similarity	NPC88363
0.7433	Intermediate Similarity	NPC176199
0.7433	Intermediate Similarity	NPC215795
0.7426	Intermediate Similarity	NPC469743
0.7421	Intermediate Similarity	NPC94943
0.7415	Intermediate Similarity	NPC471284
0.7413	Intermediate Similarity	NPC225821
0.7407	Intermediate Similarity	NPC163055
0.7407	Intermediate Similarity	NPC469358
0.7405	Intermediate Similarity	NPC313791
0.7405	Intermediate Similarity	NPC472123
0.7404	Intermediate Similarity	NPC61813
0.738	Intermediate Similarity	NPC211997
0.738	Intermediate Similarity	NPC248454
0.7379	Intermediate Similarity	NPC476114
0.7371	Intermediate Similarity	NPC55493
0.7366	Intermediate Similarity	NPC37423
0.7366	Intermediate Similarity	NPC275305
0.7365	Intermediate Similarity	NPC22079
0.7363	Intermediate Similarity	NPC18661
0.7363	Intermediate Similarity	NPC277350
0.7358	Intermediate Similarity	NPC329858
0.7356	Intermediate Similarity	NPC242446
0.7356	Intermediate Similarity	NPC475476
0.7351	Intermediate Similarity	NPC126492
0.734	Intermediate Similarity	NPC213468
0.733	Intermediate Similarity	NPC62510
0.733	Intermediate Similarity	NPC473650
0.733	Intermediate Similarity	NPC280290
0.733	Intermediate Similarity	NPC15102
0.733	Intermediate Similarity	NPC160527
0.7326	Intermediate Similarity	NPC56618
0.7326	Intermediate Similarity	NPC134586
0.7323	Intermediate Similarity	NPC241024
0.732	Intermediate Similarity	NPC243716
0.7317	Intermediate Similarity	NPC151976
0.7317	Intermediate Similarity	NPC475778
0.7316	Intermediate Similarity	NPC212535
0.7316	Intermediate Similarity	NPC48938
0.7316	Intermediate Similarity	NPC472110
0.7316	Intermediate Similarity	NPC472109
0.7311	Intermediate Similarity	NPC472762
0.731	Intermediate Similarity	NPC70956
0.731	Intermediate Similarity	NPC229332
0.731	Intermediate Similarity	NPC243834
0.7308	Intermediate Similarity	NPC82070
0.7308	Intermediate Similarity	NPC469594
0.7306	Intermediate Similarity	NPC246700
0.7304	Intermediate Similarity	NPC234999
0.7304	Intermediate Similarity	NPC126066
0.7302	Intermediate Similarity	NPC91179
0.73	Intermediate Similarity	NPC476874
0.73	Intermediate Similarity	NPC475112
0.73	Intermediate Similarity	NPC475085
0.73	Intermediate Similarity	NPC291535
0.7299	Intermediate Similarity	NPC475271
0.7297	Intermediate Similarity	NPC194411
0.7296	Intermediate Similarity	NPC195314
0.7296	Intermediate Similarity	NPC181502
0.7296	Intermediate Similarity	NPC85066
0.7295	Intermediate Similarity	NPC74969
0.7295	Intermediate Similarity	NPC204491
0.7293	Intermediate Similarity	NPC92796
0.7293	Intermediate Similarity	NPC230869
0.7293	Intermediate Similarity	NPC135141

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 NPC46413 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	170
0.1-0.2	525
0.2-0.3	748
0.3-0.4	1540
0.4-0.5	3211
0.5-0.6	2362
0.6-0.7	528
0.7-0.8	66
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8079	Intermediate Similarity	NPD1326	Approved
0.8079	Intermediate Similarity	NPD1325	Approved
0.8056	Intermediate Similarity	NPD2144	Approved
0.7923	Intermediate Similarity	NPD3038	Discontinued
0.7784	Intermediate Similarity	NPD5596	Phase 2
0.7717	Intermediate Similarity	NPD8386	Phase 2
0.7647	Intermediate Similarity	NPD1592	Phase 3
0.7609	Intermediate Similarity	NPD2381	Approved
0.7609	Intermediate Similarity	NPD2380	Approved
0.7609	Intermediate Similarity	NPD2382	Approved
0.7581	Intermediate Similarity	NPD8464	Clinical (unspecified phase)
0.755	Intermediate Similarity	NPD7947	Clinical (unspecified phase)
0.7543	Intermediate Similarity	NPD4462	Approved
0.7543	Intermediate Similarity	NPD4463	Approved
0.7527	Intermediate Similarity	NPD4079	Approved
0.7527	Intermediate Similarity	NPD4076	Approved
0.7514	Intermediate Similarity	NPD5744	Clinical (unspecified phase)
0.7513	Intermediate Similarity	NPD6610	Clinical (unspecified phase)
0.7487	Intermediate Similarity	NPD6595	Phase 3
0.7486	Intermediate Similarity	NPD4184	Clinical (unspecified phase)
0.7473	Intermediate Similarity	NPD3505	Approved
0.7473	Intermediate Similarity	NPD3506	Approved
0.7459	Intermediate Similarity	NPD5065	Approved
0.7459	Intermediate Similarity	NPD5140	Approved
0.7459	Intermediate Similarity	NPD5138	Approved
0.7448	Intermediate Similarity	NPD4499	Approved
0.743	Intermediate Similarity	NPD4671	Clinical (unspecified phase)
0.743	Intermediate Similarity	NPD4669	Clinical (unspecified phase)
0.743	Intermediate Similarity	NPD4670	Clinical (unspecified phase)
0.7363	Intermediate Similarity	NPD7957	Phase 1
0.7363	Intermediate Similarity	NPD7958	Clinical (unspecified phase)
0.7358	Intermediate Similarity	NPD2564	Approved
0.7358	Intermediate Similarity	NPD2565	Phase 2
0.7345	Intermediate Similarity	NPD2172	Phase 1
0.7344	Intermediate Similarity	NPD8431	Approved
0.7337	Intermediate Similarity	NPD4511	Phase 1
0.7337	Intermediate Similarity	NPD2844	Phase 3
0.7323	Intermediate Similarity	NPD6248	Phase 2
0.7323	Intermediate Similarity	NPD6249	Phase 2
0.732	Intermediate Similarity	NPD5913	Phase 3
0.732	Intermediate Similarity	NPD5912	Clinical (unspecified phase)
0.732	Intermediate Similarity	NPD6630	Clinical (unspecified phase)
0.7316	Intermediate Similarity	NPD5728	Clinical (unspecified phase)
0.731	Intermediate Similarity	NPD7948	Phase 1
0.731	Intermediate Similarity	NPD5003	Discontinued
0.7303	Intermediate Similarity	NPD6158	Phase 2
0.7303	Intermediate Similarity	NPD6476	Clinical (unspecified phase)
0.7288	Intermediate Similarity	NPD3100	Discontinued
0.7277	Intermediate Similarity	NPD3003	Approved
0.7277	Intermediate Similarity	NPD4862	Clinical (unspecified phase)
0.7268	Intermediate Similarity	NPD7470	Discontinued
0.7247	Intermediate Similarity	NPD3835	Phase 3
0.7247	Intermediate Similarity	NPD3833	Phase 3
0.7243	Intermediate Similarity	NPD5021	Discontinued
0.7243	Intermediate Similarity	NPD5069	Clinical (unspecified phase)
0.7228	Intermediate Similarity	NPD5901	Discontinued
0.7214	Intermediate Similarity	NPD8073	Approved
0.7213	Intermediate Similarity	NPD972	Clinical (unspecified phase)
0.7207	Intermediate Similarity	NPD2882	Phase 1
0.7196	Intermediate Similarity	NPD6978	Phase 2
0.7196	Intermediate Similarity	NPD6977	Clinical (unspecified phase)
0.7196	Intermediate Similarity	NPD6203	Clinical (unspecified phase)
0.7183	Intermediate Similarity	NPD6976	Clinical (unspecified phase)
0.7178	Intermediate Similarity	NPD8072	Approved
0.7172	Intermediate Similarity	NPD6449	Clinical (unspecified phase)
0.7165	Intermediate Similarity	NPD6141	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD8036	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD8037	Clinical (unspecified phase)
0.7157	Intermediate Similarity	NPD5575	Clinical (unspecified phase)
0.7151	Intermediate Similarity	NPD4640	Approved
0.7151	Intermediate Similarity	NPD4638	Approved
0.7151	Intermediate Similarity	NPD4639	Approved
0.715	Intermediate Similarity	NPD1768	Approved
0.715	Intermediate Similarity	NPD3330	Phase 1
0.7135	Intermediate Similarity	NPD2094	Phase 2
0.7135	Intermediate Similarity	NPD2092	Phase 2
0.7135	Intermediate Similarity	NPD2095	Phase 2
0.7129	Intermediate Similarity	NPD5612	Discontinued
0.7128	Intermediate Similarity	NPD8110	Clinical (unspecified phase)
0.7114	Intermediate Similarity	NPD4601	Approved
0.7114	Intermediate Similarity	NPD4600	Approved
0.7104	Intermediate Similarity	NPD1554	Clinical (unspecified phase)
0.7098	Intermediate Similarity	NPD2096	Phase 2
0.7098	Intermediate Similarity	NPD2091	Phase 2
0.7094	Intermediate Similarity	NPD5487	Phase 1
0.7094	Intermediate Similarity	NPD6176	Phase 1
0.7092	Intermediate Similarity	NPD6281	Approved
0.709	Intermediate Similarity	NPD482	Approved
0.7081	Intermediate Similarity	NPD8112	Clinical (unspecified phase)
0.7077	Intermediate Similarity	NPD2383	Phase 1
0.7073	Intermediate Similarity	NPD8322	Phase 2
0.7065	Intermediate Similarity	NPD3800	Clinical (unspecified phase)
0.7062	Intermediate Similarity	NPD6344	Clinical (unspecified phase)
0.7062	Intermediate Similarity	NPD5254	Discontinued
0.7056	Intermediate Similarity	NPD3785	Clinical (unspecified phase)
0.7053	Intermediate Similarity	NPD749	Clinical (unspecified phase)
0.7041	Intermediate Similarity	NPD4334	Discontinued
0.7039	Intermediate Similarity	NPD2510	Approved
0.7039	Intermediate Similarity	NPD2509	Approved
0.7037	Intermediate Similarity	NPD4112	Clinical (unspecified phase)
0.7035	Intermediate Similarity	NPD3791	Clinical (unspecified phase)
0.7031	Intermediate Similarity	NPD5897	Approved
0.7031	Intermediate Similarity	NPD5899	Approved
0.7031	Intermediate Similarity	NPD5898	Approved
0.7028	Intermediate Similarity	NPD6455	Phase 3
0.7019	Intermediate Similarity	NPD6220	Phase 3
0.7019	Intermediate Similarity	NPD5066	Phase 2
0.7019	Intermediate Similarity	NPD5067	Phase 2
0.7016	Intermediate Similarity	NPD8123	Approved
0.7016	Intermediate Similarity	NPD8122	Approved
0.701	Intermediate Similarity	NPD2920	Discontinued
0.701	Intermediate Similarity	NPD4957	Phase 2
0.7005	Intermediate Similarity	NPD5835	Phase 3
0.7005	Intermediate Similarity	NPD2125	Clinical (unspecified phase)
0.7005	Intermediate Similarity	NPD5834	Phase 3
0.7	Intermediate Similarity	NPD5902	Approved
0.7	Intermediate Similarity	NPD6492	Phase 2
0.7	Intermediate Similarity	NPD5903	Approved
0.6995	Remote Similarity	NPD6717	Clinical (unspecified phase)
0.6989	Remote Similarity	NPD3943	Clinical (unspecified phase)
0.6985	Remote Similarity	NPD1304	Clinical (unspecified phase)
0.6985	Remote Similarity	NPD1038	Approved
0.698	Remote Similarity	NPD7621	Clinical (unspecified phase)
0.698	Remote Similarity	NPD4118	Clinical (unspecified phase)
0.6974	Remote Similarity	NPD5075	Discontinued
0.6968	Remote Similarity	NPD2185	Clinical (unspecified phase)
0.6965	Remote Similarity	NPD6206	Phase 1
0.6963	Remote Similarity	NPD5104	Approved
0.6944	Remote Similarity	NPD4702	Approved
0.6944	Remote Similarity	NPD4703	Approved
0.6942	Remote Similarity	NPD4901	Clinical (unspecified phase)
0.6935	Remote Similarity	NPD3404	Approved
0.6932	Remote Similarity	NPD786	Approved
0.6931	Remote Similarity	NPD6261	Phase 3
0.6927	Remote Similarity	NPD6159	Phase 2
0.6915	Remote Similarity	NPD2639	Approved
0.6915	Remote Similarity	NPD2642	Approved
0.6911	Remote Similarity	NPD4128	Approved
0.691	Remote Similarity	NPD3525	Discontinued
0.6908	Remote Similarity	NPD1392	Approved
0.6905	Remote Similarity	NPD7594	Clinical (unspecified phase)
0.6898	Remote Similarity	NPD7716	Approved
0.6898	Remote Similarity	NPD7717	Approved
0.6897	Remote Similarity	NPD8395	Approved
0.6897	Remote Similarity	NPD2177	Approved
0.6897	Remote Similarity	NPD2176	Approved
0.6897	Remote Similarity	NPD8396	Approved
0.6897	Remote Similarity	NPD2175	Phase 3
0.6895	Remote Similarity	NPD7824	Approved
0.6889	Remote Similarity	NPD1683	Approved
0.6878	Remote Similarity	NPD5721	Clinical (unspecified phase)
0.6875	Remote Similarity	NPD5100	Phase 3
0.6872	Remote Similarity	NPD5522	Clinical (unspecified phase)
0.6869	Remote Similarity	NPD7234	Approved
0.6869	Remote Similarity	NPD7233	Approved
0.6866	Remote Similarity	NPD7271	Approved
0.6863	Remote Similarity	NPD4501	Approved
0.6863	Remote Similarity	NPD484	Approved
0.6863	Remote Similarity	NPD4500	Approved
0.6862	Remote Similarity	NPD2915	Discontinued
0.686	Remote Similarity	NPD8403	Phase 1
0.686	Remote Similarity	NPD6732	Clinical (unspecified phase)
0.6859	Remote Similarity	NPD750	Phase 2
0.6856	Remote Similarity	NPD6452	Discontinued
0.6854	Remote Similarity	NPD3834	Clinical (unspecified phase)
0.6853	Remote Similarity	NPD5444	Phase 1
0.685	Remote Similarity	NPD4315	Phase 2
0.6847	Remote Similarity	NPD7946	Pre-registration
0.6847	Remote Similarity	NPD7889	Clinical (unspecified phase)
0.684	Remote Similarity	NPD7073	Clinical (unspecified phase)
0.684	Remote Similarity	NPD4897	Phase 2
0.6832	Remote Similarity	NPD7935	Phase 2
0.6828	Remote Similarity	NPD5255	Approved
0.6825	Remote Similarity	NPD8093	Discontinued
0.6821	Remote Similarity	NPD4204	Approved
0.6821	Remote Similarity	NPD4203	Approved
0.6818	Remote Similarity	NPD4948	Discontinued
0.6818	Remote Similarity	NPD3961	Discontinued
0.6814	Remote Similarity	NPD3814	Phase 1
0.6813	Remote Similarity	NPD4374	Clinical (unspecified phase)
0.681	Remote Similarity	NPD4900	Clinical (unspecified phase)
0.681	Remote Similarity	NPD7825	Clinical (unspecified phase)
0.681	Remote Similarity	NPD7809	Clinical (unspecified phase)
0.6804	Remote Similarity	NPD7731	Approved
0.6804	Remote Similarity	NPD7730	Approved
0.6802	Remote Similarity	NPD7424	Clinical (unspecified phase)
0.68	Remote Similarity	NPD5592	Clinical (unspecified phase)
0.6794	Remote Similarity	NPD8399	Phase 1
0.6794	Remote Similarity	NPD8423	Phase 2
0.6791	Remote Similarity	NPD1403	Approved
0.6791	Remote Similarity	NPD1404	Approved
0.6789	Remote Similarity	NPD2640	Approved
0.6789	Remote Similarity	NPD5862	Discovery
0.6789	Remote Similarity	NPD2641	Approved
0.6788	Remote Similarity	NPD6375	Clinical (unspecified phase)
0.6788	Remote Similarity	NPD4075	Phase 2
0.6782	Remote Similarity	NPD3324	Clinical (unspecified phase)
0.6782	Remote Similarity	NPD4602	Approved
0.6779	Remote Similarity	NPD7001	Phase 3
0.6777	Remote Similarity	NPD5936	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