NPASS Compound

Structure

CID1108 OpenBabel06191715322D 28 32 0 0 1 0 0 0 0 0999 V2000 6.7698 2.7396 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3801 -1.1554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1006 1.9965 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6730 -0.4483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1225 2.2044 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0518 3.9849 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9428 3.5310 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7071 -0.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7869 3.4403 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9951 2.5323 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4533 1.4612 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7346 2.4417 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7321 1.0000 0.0000 C 0 0 0 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 0.1564 1.9877 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4752 1.6691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4417 1.7346 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0739 2.4781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4294 1.8910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4048 3.2213 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0685 2.5827 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9877 0.8436 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 1 0 0 0 0 2 4 1 0 0 0 0 3 5 1 0 0 0 0 4 8 1 0 0 0 0 5 11 1 0 0 0 0 6 7 1 0 0 0 0 6 9 2 0 0 0 0 7 10 1 0 0 0 0 8 17 1 0 0 0 0 9 15 1 0 0 0 0 10 18 1 0 0 0 0 11 19 2 0 0 0 0 12 13 1 0 0 0 0 13 16 1 0 0 0 0 14 12 1 6 0 0 0 14 17 1 0 0 0 0 14 21 1 0 0 0 0 15 18 2 0 0 0 0 15 22 1 0 0 0 0 16 19 1 0 0 0 0 16 20 2 0 0 0 0 17 24 1 6 0 0 0 19 27 1 0 0 0 0 20 21 1 0 0 0 0 20 23 1 0 0 0 0 21 24 1 6 0 0 0 22 25 2 0 0 0 0 22 28 1 0 0 0 0 23 26 2 0 0 0 0 23 27 1 0 0 0 0 24 18 1 1 0 0 0 24 28 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	380.2
Volume:	400.22
LogP:	6.222
LogD:	5.338
LogS:	-5.444
# Rotatable Bonds:	4
TPSA:	59.67
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.708
Synthetic Accessibility Score:	5.47
Fsp3:	0.542
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.898
MDCK Permeability:	2.6485689886612818e-05
Pgp-inhibitor:	0.538
Pgp-substrate:	0.211
Human Intestinal Absorption (HIA):	0.027
20% Bioavailability (F20%):	0.901
30% Bioavailability (F30%):	0.402

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.126
Plasma Protein Binding (PPB):	99.13323211669922%
Volume Distribution (VD):	2.733
Pgp-substrate:	2.5162482261657715%

ADMET: Metabolism

CYP1A2-inhibitor:	0.809
CYP1A2-substrate:	0.653
CYP2C19-inhibitor:	0.696
CYP2C19-substrate:	0.673
CYP2C9-inhibitor:	0.909
CYP2C9-substrate:	0.856
CYP2D6-inhibitor:	0.442
CYP2D6-substrate:	0.609
CYP3A4-inhibitor:	0.73
CYP3A4-substrate:	0.185

ADMET: Excretion

Clearance (CL):	10.095
Half-life (T1/2):	0.046

ADMET: Toxicity

hERG Blockers:	0.494
Human Hepatotoxicity (H-HT):	0.867
Drug-inuced Liver Injury (DILI):	0.504
AMES Toxicity:	0.017
Rat Oral Acute Toxicity:	0.953
Maximum Recommended Daily Dose:	0.896
Skin Sensitization:	0.947
Carcinogencity:	0.914
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.978

Download Data

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

Natural Product: NPC1108

Natural Product ID:	NPC1108
*Common Name:**	(3S,3'z,5'ar,6's,7'as)-3'-Butylidene-6'-Propylspiro[4,5-Dihydro-2-Benzofuran-3,7'-5,5A,6,7A-Tetrahydro-4H-Cyclobuta[G][2]Benzofuran]-1,1'-Dione
IUPAC Name:	(3S,3'Z,5'aR,6'S,7'aS)-3'-butylidene-6'-propylspiro[4,5-dihydro-2-benzofuran-3,7'-5,5a,6,7a-tetrahydro-4H-cyclobuta[g][2]benzofuran]-1,1'-dione
Synonyms:
Standard InCHIKey:	TYSOMZQRYGBSKN-DRQJQJQISA-N
Standard InCHI:	InChI=1S/C24H28O4/c1-3-5-11-19-16-13-12-14-17(8-4-2)24(21(14)20(16)23(26)27-19)18-10-7-6-9-15(18)22(25)28-24/h6,9,11,14,17,21H,3-5,7-8,10,12-13H2,1-2H3/b19-11-/t14-,17+,21+,24-/m1/s1
SMILES:	CCC/C=C1/C2=C([C@@H]3[C@H](CC2)[C@H](CCC)[C@]23C3=C(C=CCC3)C(=O)O2)C(=O)O1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2047346
PubChem CID:	6442656
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0003408] Isobenzofurans

*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
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[11374978]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15679317]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	roots	purchased from Kiu Shun Trading Ltd., Vancouver, Canada	2000	PMID[16643021]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	root	n.a.	PMID[17997069]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25538068]
NPO18951	Ligusticum sinense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26521454]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27400088]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22033	Cnidium officinale	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18951	Ligusticum sinense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22033	Cnidium officinale	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18951	Ligusticum sinense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18951	Ligusticum sinense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2154	Ligusticum tenuissimum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO18951	Ligusticum sinense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11438	Angelica gigas	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22033	Cnidium officinale	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO18951	Ligusticum sinense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2921	Angelica acutiloba	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15462	Angelica sinensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11438	Angelica gigas	Species	Apiaceae	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	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT111	Cell Line	K562	Homo sapiens	IC50	=	46100.0	nM	PMID[448526]
NPT148	Cell Line	HCT-15	Homo sapiens	IC50	=	44800.0	nM	PMID[448526]
NPT311	Cell Line	SK-LU-1	Homo sapiens	IC50	=	13200.0	nM	PMID[448526]

☑ 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 NPC1108 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	254
0.1-0.2	1307
0.2-0.3	5008
0.3-0.4	13401
0.4-0.5	14332
0.5-0.6	6556
0.6-0.7	1750
0.7-0.8	88
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8261	Intermediate Similarity	NPC472302
0.8085	Intermediate Similarity	NPC469372
0.8021	Intermediate Similarity	NPC477130
0.8021	Intermediate Similarity	NPC477129
0.7979	Intermediate Similarity	NPC284561
0.7979	Intermediate Similarity	NPC173042
0.7938	Intermediate Similarity	NPC295347
0.7938	Intermediate Similarity	NPC127197
0.7895	Intermediate Similarity	NPC212679
0.7895	Intermediate Similarity	NPC469595
0.7895	Intermediate Similarity	NPC220454
0.7872	Intermediate Similarity	NPC226863
0.7778	Intermediate Similarity	NPC208094
0.7745	Intermediate Similarity	NPC271059
0.7745	Intermediate Similarity	NPC25666
0.7742	Intermediate Similarity	NPC189311
0.7732	Intermediate Similarity	NPC475657
0.7717	Intermediate Similarity	NPC193198
0.7714	Intermediate Similarity	NPC137911
0.7714	Intermediate Similarity	NPC228477
0.7684	Intermediate Similarity	NPC477128
0.7653	Intermediate Similarity	NPC38830
0.764	Intermediate Similarity	NPC54996
0.7629	Intermediate Similarity	NPC166110
0.7609	Intermediate Similarity	NPC186276
0.7609	Intermediate Similarity	NPC268122
0.7579	Intermediate Similarity	NPC181327
0.7576	Intermediate Similarity	NPC171395
0.7551	Intermediate Similarity	NPC248193
0.7549	Intermediate Similarity	NPC244456
0.7549	Intermediate Similarity	NPC469657
0.7527	Intermediate Similarity	NPC22611
0.7527	Intermediate Similarity	NPC118423
0.7526	Intermediate Similarity	NPC280592
0.7526	Intermediate Similarity	NPC253177
0.7526	Intermediate Similarity	NPC213636
0.75	Intermediate Similarity	NPC112654
0.75	Intermediate Similarity	NPC42470
0.7474	Intermediate Similarity	NPC168248
0.7451	Intermediate Similarity	NPC54705
0.7449	Intermediate Similarity	NPC193396
0.7449	Intermediate Similarity	NPC296114
0.7449	Intermediate Similarity	NPC65513
0.7449	Intermediate Similarity	NPC32944
0.7449	Intermediate Similarity	NPC471329
0.7447	Intermediate Similarity	NPC30486
0.7444	Intermediate Similarity	NPC473825
0.7429	Intermediate Similarity	NPC477125
0.7429	Intermediate Similarity	NPC34768
0.7426	Intermediate Similarity	NPC84335
0.7426	Intermediate Similarity	NPC38530
0.7423	Intermediate Similarity	NPC5509
0.7423	Intermediate Similarity	NPC142159
0.7423	Intermediate Similarity	NPC36668
0.7423	Intermediate Similarity	NPC118011
0.7423	Intermediate Similarity	NPC95364
0.7419	Intermediate Similarity	NPC200513
0.74	Intermediate Similarity	NPC473369
0.74	Intermediate Similarity	NPC209355
0.7396	Intermediate Similarity	NPC312561
0.7391	Intermediate Similarity	NPC195424
0.7358	Intermediate Similarity	NPC302788
0.7347	Intermediate Similarity	NPC281942
0.7347	Intermediate Similarity	NPC232426
0.7333	Intermediate Similarity	NPC476001
0.7333	Intermediate Similarity	NPC474898
0.7327	Intermediate Similarity	NPC301596
0.7327	Intermediate Similarity	NPC299396
0.7327	Intermediate Similarity	NPC172998
0.732	Intermediate Similarity	NPC478261
0.732	Intermediate Similarity	NPC473658
0.732	Intermediate Similarity	NPC478260
0.732	Intermediate Similarity	NPC478259
0.732	Intermediate Similarity	NPC215831
0.732	Intermediate Similarity	NPC26078
0.732	Intermediate Similarity	NPC196407
0.7308	Intermediate Similarity	NPC273005
0.7308	Intermediate Similarity	NPC235369
0.7308	Intermediate Similarity	NPC469606
0.7308	Intermediate Similarity	NPC31058
0.7292	Intermediate Similarity	NPC220478
0.7273	Intermediate Similarity	NPC141831
0.7263	Intermediate Similarity	NPC159635
0.7255	Intermediate Similarity	NPC53844
0.7255	Intermediate Similarity	NPC110937
0.7255	Intermediate Similarity	NPC476253
0.7255	Intermediate Similarity	NPC202705
0.7253	Intermediate Similarity	NPC187568
0.7253	Intermediate Similarity	NPC103987
0.7253	Intermediate Similarity	NPC53581
0.7253	Intermediate Similarity	NPC316500
0.7253	Intermediate Similarity	NPC41780
0.7253	Intermediate Similarity	NPC316324
0.7245	Intermediate Similarity	NPC307092
0.7245	Intermediate Similarity	NPC73995
0.7245	Intermediate Similarity	NPC285982
0.7245	Intermediate Similarity	NPC168131
0.7245	Intermediate Similarity	NPC51358
0.7241	Intermediate Similarity	NPC265574
0.7241	Intermediate Similarity	NPC232812
0.7234	Intermediate Similarity	NPC35556
0.7234	Intermediate Similarity	NPC94200
0.7228	Intermediate Similarity	NPC273197
0.7228	Intermediate Similarity	NPC234339
0.7228	Intermediate Similarity	NPC31021
0.7216	Intermediate Similarity	NPC75315
0.7216	Intermediate Similarity	NPC163016
0.7216	Intermediate Similarity	NPC477228
0.7212	Intermediate Similarity	NPC473384
0.7212	Intermediate Similarity	NPC168319
0.7212	Intermediate Similarity	NPC194028
0.72	Intermediate Similarity	NPC471571
0.72	Intermediate Similarity	NPC476597
0.72	Intermediate Similarity	NPC476598
0.7196	Intermediate Similarity	NPC179380
0.7188	Intermediate Similarity	NPC147921
0.7188	Intermediate Similarity	NPC215364
0.7188	Intermediate Similarity	NPC65661
0.7188	Intermediate Similarity	NPC78089
0.7174	Intermediate Similarity	NPC471220
0.7174	Intermediate Similarity	NPC128276
0.717	Intermediate Similarity	NPC189616
0.7159	Intermediate Similarity	NPC64234
0.7159	Intermediate Similarity	NPC37929
0.7157	Intermediate Similarity	NPC260796
0.7157	Intermediate Similarity	NPC311166
0.7143	Intermediate Similarity	NPC123360
0.7143	Intermediate Similarity	NPC193843
0.7143	Intermediate Similarity	NPC72397
0.7143	Intermediate Similarity	NPC475320
0.7143	Intermediate Similarity	NPC476081
0.7143	Intermediate Similarity	NPC24816
0.7143	Intermediate Similarity	NPC473223
0.7143	Intermediate Similarity	NPC471956
0.7143	Intermediate Similarity	NPC249889
0.7129	Intermediate Similarity	NPC166143
0.7129	Intermediate Similarity	NPC476596
0.7129	Intermediate Similarity	NPC120351
0.7129	Intermediate Similarity	NPC471994
0.7129	Intermediate Similarity	NPC56525
0.7129	Intermediate Similarity	NPC476415
0.7129	Intermediate Similarity	NPC470697
0.7128	Intermediate Similarity	NPC325031
0.7128	Intermediate Similarity	NPC471325
0.7128	Intermediate Similarity	NPC141810
0.7128	Intermediate Similarity	NPC282293
0.7115	Intermediate Similarity	NPC477720
0.7113	Intermediate Similarity	NPC107787
0.7113	Intermediate Similarity	NPC234038
0.7111	Intermediate Similarity	NPC306928
0.7103	Intermediate Similarity	NPC478052
0.7103	Intermediate Similarity	NPC469607
0.71	Intermediate Similarity	NPC45579
0.71	Intermediate Similarity	NPC204341
0.71	Intermediate Similarity	NPC289479
0.71	Intermediate Similarity	NPC303697
0.71	Intermediate Similarity	NPC49420
0.7097	Intermediate Similarity	NPC178277
0.7091	Intermediate Similarity	NPC179798
0.7091	Intermediate Similarity	NPC304180
0.7087	Intermediate Similarity	NPC257726
0.7087	Intermediate Similarity	NPC204054
0.7083	Intermediate Similarity	NPC71626
0.7083	Intermediate Similarity	NPC475100
0.7083	Intermediate Similarity	NPC196487
0.7083	Intermediate Similarity	NPC14575
0.7083	Intermediate Similarity	NPC149869
0.7075	Intermediate Similarity	NPC132395
0.7075	Intermediate Similarity	NPC471365
0.7075	Intermediate Similarity	NPC471364
0.7071	Intermediate Similarity	NPC310236
0.7071	Intermediate Similarity	NPC212598
0.7071	Intermediate Similarity	NPC280833
0.7071	Intermediate Similarity	NPC471654
0.7071	Intermediate Similarity	NPC106040
0.7071	Intermediate Similarity	NPC115179
0.7071	Intermediate Similarity	NPC174342
0.7065	Intermediate Similarity	NPC57744
0.7059	Intermediate Similarity	NPC183012
0.7059	Intermediate Similarity	NPC20546
0.7059	Intermediate Similarity	NPC33473
0.7053	Intermediate Similarity	NPC178676
0.7053	Intermediate Similarity	NPC173609
0.7053	Intermediate Similarity	NPC471218
0.7048	Intermediate Similarity	NPC146822
0.7048	Intermediate Similarity	NPC474912
0.7048	Intermediate Similarity	NPC469851
0.7048	Intermediate Similarity	NPC474899
0.7041	Intermediate Similarity	NPC171722
0.7041	Intermediate Similarity	NPC125925
0.7041	Intermediate Similarity	NPC160138
0.7041	Intermediate Similarity	NPC475703
0.7037	Intermediate Similarity	NPC469853
0.7033	Intermediate Similarity	NPC244166
0.703	Intermediate Similarity	NPC115021
0.703	Intermediate Similarity	NPC166346
0.703	Intermediate Similarity	NPC472303
0.703	Intermediate Similarity	NPC242069
0.703	Intermediate Similarity	NPC469939
0.7021	Intermediate Similarity	NPC268827

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 NPC1108 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	240
0.1-0.2	1535
0.2-0.3	3719
0.3-0.4	2519
0.4-0.5	881
0.5-0.6	229
0.6-0.7	27
0.7-0.8	0
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
0.7526	Intermediate Similarity	NPD5207	Approved
0.7419	Intermediate Similarity	NPD4752	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD5694	Approved
0.7273	Intermediate Similarity	NPD5281	Approved
0.7273	Intermediate Similarity	NPD5284	Approved
0.7172	Intermediate Similarity	NPD5692	Phase 3
0.71	Intermediate Similarity	NPD5693	Phase 1
0.71	Intermediate Similarity	NPD6050	Approved
0.701	Intermediate Similarity	NPD1694	Approved
0.6875	Remote Similarity	NPD6053	Discontinued
0.6848	Remote Similarity	NPD8039	Approved
0.6733	Remote Similarity	NPD6080	Approved
0.6733	Remote Similarity	NPD6904	Approved
0.6733	Remote Similarity	NPD6673	Approved
0.6733	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.6731	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6731	Remote Similarity	NPD5654	Approved
0.67	Remote Similarity	NPD3573	Approved
0.6699	Remote Similarity	NPD5779	Approved
0.6699	Remote Similarity	NPD5778	Approved
0.6635	Remote Similarity	NPD6001	Approved
0.6634	Remote Similarity	NPD5737	Approved
0.6634	Remote Similarity	NPD6903	Approved
0.6634	Remote Similarity	NPD6672	Approved
0.6634	Remote Similarity	NPD5208	Approved
0.6604	Remote Similarity	NPD5959	Approved
0.66	Remote Similarity	NPD7146	Approved
0.66	Remote Similarity	NPD5330	Approved
0.66	Remote Similarity	NPD7334	Approved
0.66	Remote Similarity	NPD6409	Approved
0.66	Remote Similarity	NPD7521	Approved
0.66	Remote Similarity	NPD6684	Approved
0.6571	Remote Similarity	NPD5695	Phase 3
0.6569	Remote Similarity	NPD6101	Approved
0.6569	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6538	Remote Similarity	NPD6399	Phase 3
0.6486	Remote Similarity	NPD6008	Approved
0.6476	Remote Similarity	NPD7900	Approved
0.6476	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6442	Remote Similarity	NPD6411	Approved
0.6436	Remote Similarity	NPD4694	Approved
0.6436	Remote Similarity	NPD4519	Discontinued
0.6436	Remote Similarity	NPD4623	Approved
0.6436	Remote Similarity	NPD5280	Approved
0.6436	Remote Similarity	NPD6098	Approved
0.6429	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6415	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6408	Remote Similarity	NPD1695	Approved
0.6389	Remote Similarity	NPD5696	Approved
0.6383	Remote Similarity	NPD4687	Approved
0.6364	Remote Similarity	NPD5209	Approved
0.6356	Remote Similarity	NPD7115	Discovery
0.6354	Remote Similarity	NPD4756	Discovery
0.6327	Remote Similarity	NPD4695	Discontinued
0.6321	Remote Similarity	NPD5282	Discontinued
0.6311	Remote Similarity	NPD4518	Approved
0.6306	Remote Similarity	NPD6052	Approved
0.63	Remote Similarity	NPD7154	Phase 3
0.6296	Remote Similarity	NPD6083	Phase 2
0.6296	Remote Similarity	NPD6084	Phase 2
0.6296	Remote Similarity	NPD7902	Approved
0.6275	Remote Similarity	NPD5690	Phase 2
0.6261	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6261	Remote Similarity	NPD2067	Discontinued
0.625	Remote Similarity	NPD6051	Approved
0.6239	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6239	Remote Similarity	NPD7638	Approved
0.6239	Remote Similarity	NPD4225	Approved
0.6228	Remote Similarity	NPD6686	Approved
0.622	Remote Similarity	NPD7260	Phase 2
0.6211	Remote Similarity	NPD5733	Approved
0.6211	Remote Similarity	NPD4058	Approved
0.62	Remote Similarity	NPD4223	Phase 3
0.62	Remote Similarity	NPD4221	Approved
0.619	Remote Similarity	NPD6698	Approved
0.619	Remote Similarity	NPD5785	Approved
0.619	Remote Similarity	NPD46	Approved
0.6182	Remote Similarity	NPD7639	Approved
0.6182	Remote Similarity	NPD6404	Discontinued
0.6182	Remote Similarity	NPD7640	Approved
0.6174	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.617	Remote Similarity	NPD5276	Approved
0.6168	Remote Similarity	NPD7748	Approved
0.614	Remote Similarity	NPD5697	Approved
0.614	Remote Similarity	NPD6614	Approved
0.614	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6139	Remote Similarity	NPD5362	Discontinued
0.6117	Remote Similarity	NPD5279	Phase 3
0.6117	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6106	Remote Similarity	NPD5909	Discontinued
0.6087	Remote Similarity	NPD6011	Approved
0.6087	Remote Similarity	NPD6881	Approved
0.6087	Remote Similarity	NPD7320	Approved
0.6087	Remote Similarity	NPD6899	Approved
0.6078	Remote Similarity	NPD4197	Approved
0.6068	Remote Similarity	NPD6650	Approved
0.6068	Remote Similarity	NPD6649	Approved
0.6053	Remote Similarity	NPD6675	Approved
0.6053	Remote Similarity	NPD7128	Approved
0.6053	Remote Similarity	NPD6402	Approved
0.6053	Remote Similarity	NPD5739	Approved
0.6044	Remote Similarity	NPD2685	Clinical (unspecified phase)
0.6038	Remote Similarity	NPD7838	Discovery
0.6038	Remote Similarity	NPD4096	Approved
0.6036	Remote Similarity	NPD6648	Approved
0.6034	Remote Similarity	NPD6012	Approved
0.6034	Remote Similarity	NPD6014	Approved
0.6034	Remote Similarity	NPD6372	Approved
0.6034	Remote Similarity	NPD6013	Approved
0.6034	Remote Similarity	NPD6373	Approved
0.6019	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6019	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6019	Remote Similarity	NPD5363	Approved
0.6019	Remote Similarity	NPD5329	Approved
0.6	Remote Similarity	NPD5701	Approved
0.5983	Remote Similarity	NPD7290	Approved
0.5983	Remote Similarity	NPD6883	Approved
0.5983	Remote Similarity	NPD7102	Approved
0.5981	Remote Similarity	NPD7515	Phase 2
0.5968	Remote Similarity	NPD3412	Clinical (unspecified phase)
0.5963	Remote Similarity	NPD5210	Approved
0.5963	Remote Similarity	NPD4629	Approved
0.5962	Remote Similarity	NPD4688	Approved
0.5962	Remote Similarity	NPD3618	Phase 1
0.5962	Remote Similarity	NPD5205	Approved
0.5962	Remote Similarity	NPD4690	Approved
0.5962	Remote Similarity	NPD4693	Phase 3
0.5962	Remote Similarity	NPD4689	Approved
0.5962	Remote Similarity	NPD4138	Approved
0.5962	Remote Similarity	NPD4249	Approved
0.596	Remote Similarity	NPD3617	Approved
0.5957	Remote Similarity	NPD4137	Phase 3
0.5943	Remote Similarity	NPD4753	Phase 2
0.5941	Remote Similarity	NPD5369	Approved
0.5934	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.5932	Remote Similarity	NPD8130	Phase 1
0.5932	Remote Similarity	NPD6847	Approved
0.5932	Remote Similarity	NPD6869	Approved
0.5932	Remote Similarity	NPD6617	Approved
0.5926	Remote Similarity	NPD5133	Approved
0.5923	Remote Similarity	NPD6845	Suspended
0.5922	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.5922	Remote Similarity	NPD3666	Approved
0.5922	Remote Similarity	NPD3665	Phase 1
0.5922	Remote Similarity	NPD3668	Phase 3
0.5922	Remote Similarity	NPD3133	Approved
0.5909	Remote Similarity	NPD7732	Phase 3
0.5905	Remote Similarity	NPD4251	Approved
0.5905	Remote Similarity	NPD4250	Approved
0.5895	Remote Similarity	NPD4691	Approved
0.5895	Remote Similarity	NPD4747	Approved
0.5887	Remote Similarity	NPD8517	Approved
0.5887	Remote Similarity	NPD8515	Approved
0.5887	Remote Similarity	NPD8516	Approved
0.5887	Remote Similarity	NPD8513	Phase 3
0.5887	Remote Similarity	NPD7503	Approved
0.5882	Remote Similarity	NPD4269	Approved
0.5882	Remote Similarity	NPD6882	Approved
0.5882	Remote Similarity	NPD8297	Approved
0.5882	Remote Similarity	NPD3667	Approved
0.5882	Remote Similarity	NPD4270	Approved
0.5847	Remote Similarity	NPD6371	Approved
0.5842	Remote Similarity	NPD4820	Approved
0.5842	Remote Similarity	NPD4819	Approved
0.5842	Remote Similarity	NPD4821	Approved
0.5842	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.5842	Remote Similarity	NPD4822	Approved
0.5833	Remote Similarity	NPD7637	Suspended
0.5833	Remote Similarity	NPD7983	Approved
0.5827	Remote Similarity	NPD7507	Approved
0.5825	Remote Similarity	NPD3527	Clinical (unspecified phase)
0.581	Remote Similarity	NPD5786	Approved
0.5806	Remote Similarity	NPD7331	Phase 2
0.5806	Remote Similarity	NPD6108	Clinical (unspecified phase)
0.5798	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.5798	Remote Similarity	NPD2181	Clinical (unspecified phase)
0.5798	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.5794	Remote Similarity	NPD7457	Clinical (unspecified phase)
0.5789	Remote Similarity	NPD5211	Phase 2
0.578	Remote Similarity	NPD4202	Approved
0.5769	Remote Similarity	NPD4786	Approved
0.5766	Remote Similarity	NPD7614	Phase 1
0.5766	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.5763	Remote Similarity	NPD2182	Approved
0.576	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.5752	Remote Similarity	NPD4696	Approved
0.5752	Remote Similarity	NPD5285	Approved
0.5752	Remote Similarity	NPD5286	Approved
0.575	Remote Similarity	NPD1609	Clinical (unspecified phase)
0.5743	Remote Similarity	NPD4195	Approved
0.5738	Remote Similarity	NPD690	Clinical (unspecified phase)
0.573	Remote Similarity	NPD287	Approved
0.5728	Remote Similarity	NPD6435	Approved
0.5727	Remote Similarity	NPD5122	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD4755	Approved
0.5714	Remote Similarity	NPD4191	Approved
0.5714	Remote Similarity	NPD4193	Approved
0.5714	Remote Similarity	NPD4194	Approved
0.5714	Remote Similarity	NPD4192	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