NPASS Compound

Structure

CID28227 OpenBabel06191715352D 33 37 0 0 1 0 0 0 0 0999 V2000 0.3500 6.5526 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3045 6.0134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3587 -2.9380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2244 -2.4380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5187 0.5160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0006 1.9689 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0003 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6819 4.1029 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0103 4.8501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3706 3.1477 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8400 -1.4540 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6798 -1.9384 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6789 0.9694 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1970 -0.4835 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3579 0.0010 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8392 1.4538 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6781 -0.0005 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3216 5.8054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0422 2.4005 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6792 0.0005 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8398 -0.4845 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6783 0.9684 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5193 -1.4535 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1973 -1.4530 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8400 1.4534 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0055 2.5009 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3584 -1.9380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5190 -0.4840 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0003 0.9689 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 5.0635 -1.9526 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5086 3.3705 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3986 1.6158 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 18 1 0 0 0 0 2 18 1 0 0 0 0 3 27 1 0 0 0 0 4 27 1 0 0 0 0 6 29 1 0 0 0 0 8 9 1 0 0 0 0 8 10 1 0 0 0 0 9 18 2 0 0 0 0 11 12 1 0 0 0 0 11 21 2 0 0 0 0 12 23 1 0 0 0 0 13 16 1 0 0 0 0 13 20 1 0 0 0 0 14 15 1 0 0 0 0 14 24 1 0 0 0 0 15 28 1 0 0 0 0 16 29 1 0 0 0 0 17 30 1 0 0 0 0 19 10 1 6 0 0 0 19 25 1 0 0 0 0 19 26 1 0 0 0 0 20 21 1 0 0 0 0 20 28 1 6 0 0 0 21 30 1 0 0 0 0 22 17 1 6 0 0 0 22 25 1 0 0 0 0 22 33 1 0 0 0 0 23 27 1 0 0 0 0 23 28 1 6 0 0 0 24 27 1 0 0 0 0 24 31 2 0 0 0 0 25 29 1 1 0 0 0 26 32 2 0 0 0 0 26 33 1 0 0 0 0 28 5 1 6 0 0 0 29 30 1 1 0 0 0 30 7 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	452.33
Volume:	500.479
LogP:	7.404
LogD:	5.059
LogS:	-6.872
# Rotatable Bonds:	3
TPSA:	43.37
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.34
Synthetic Accessibility Score:	4.946
Fsp3:	0.8
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:	-5.025
MDCK Permeability:	2.011266587942373e-05
Pgp-inhibitor:	0.943
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.775
30% Bioavailability (F30%):	0.911

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.509
Plasma Protein Binding (PPB):	96.11957550048828%
Volume Distribution (VD):	1.469
Pgp-substrate:	3.254823684692383%

ADMET: Metabolism

CYP1A2-inhibitor:	0.052
CYP1A2-substrate:	0.296
CYP2C19-inhibitor:	0.374
CYP2C19-substrate:	0.936
CYP2C9-inhibitor:	0.356
CYP2C9-substrate:	0.238
CYP2D6-inhibitor:	0.029
CYP2D6-substrate:	0.062
CYP3A4-inhibitor:	0.865
CYP3A4-substrate:	0.809

ADMET: Excretion

Clearance (CL):	12.703
Half-life (T1/2):	0.032

ADMET: Toxicity

hERG Blockers:	0.099
Human Hepatotoxicity (H-HT):	0.451
Drug-inuced Liver Injury (DILI):	0.066
AMES Toxicity:	0.005
Rat Oral Acute Toxicity:	0.817
Maximum Recommended Daily Dose:	0.908
Skin Sensitization:	0.12
Carcinogencity:	0.195
Eye Corrosion:	0.014
Eye Irritation:	0.056
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: NPC28227

Natural Product ID:	NPC28227
*Common Name:**	Kulactone
IUPAC Name:	n.a.
Synonyms:	Kulactone
Standard InCHIKey:	ZIVZDNPCRURPNL-QCWHEMHRSA-N
Standard InCHI:	InChI=1S/C30H44O3/c1-18(2)9-8-10-19-25-22(33-26(19)32)17-30(7)21-11-12-23-27(3,4)24(31)14-15-28(23,5)20(21)13-16-29(25,30)6/h9,11,19-20,22-23,25H,8,10,12-17H2,1-7H3/t19-,20+,22+,23+,25-,28-,29+,30-/m1/s1
SMILES:	CC(=CCC[C@@H]1[C@@H]2[C@H](C[C@]3(C)C4=CC[C@H]5C(C)(C)C(=O)CC[C@]5(C)[C@H]4CC[C@@]23C)OC1=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL464664
PubChem CID:	15560423
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

*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
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	fruits	n.a.	n.a.	PMID[12467621]
NPO18596	Melia dubia	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12502333]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	Brazilian	n.a.	PMID[15387656]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	ripe fruit	n.a.	PMID[16205005]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	n.a.	root	n.a.	PMID[16212233]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	root bark	n.a.	n.a.	PMID[23282106]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	Root Bark	n.a.	n.a.	PMID[26982999]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[33253570]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[3701342]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	fruits	n.a.	n.a.	PMID[9090870]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO17823	Lycium chinense	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO18932	Melia azedarach	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18596	Melia dubia	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17823	Lycium chinense	Species	Solanaceae	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
ED50	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	ED50	=	6.2	ug ml-1	PMID[568163]

☑ 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 NPC28227 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	207
0.1-0.2	1314
0.2-0.3	6710
0.3-0.4	15465
0.4-0.5	5941
0.5-0.6	6481
0.6-0.7	5136
0.7-0.8	1330
0.8-0.85	86
0.85-0.9	17
0.9-0.95	8
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9634	High Similarity	NPC470223
0.9286	High Similarity	NPC195640
0.9277	High Similarity	NPC100391
0.9213	High Similarity	NPC322063
0.9167	High Similarity	NPC323765
0.9111	High Similarity	NPC475894
0.9011	High Similarity	NPC153792
0.9011	High Similarity	NPC271387
0.8977	High Similarity	NPC154101
0.8953	High Similarity	NPC167877
0.8889	High Similarity	NPC469599
0.8876	High Similarity	NPC470224
0.8837	High Similarity	NPC470050
0.8837	High Similarity	NPC470051
0.8837	High Similarity	NPC264127
0.8778	High Similarity	NPC472223
0.8778	High Similarity	NPC472224
0.8764	High Similarity	NPC150383
0.8721	High Similarity	NPC474218
0.8636	High Similarity	NPC472220
0.8636	High Similarity	NPC474845
0.8636	High Similarity	NPC97884
0.8632	High Similarity	NPC36321
0.8632	High Similarity	NPC140723
0.8605	High Similarity	NPC82902
0.8588	High Similarity	NPC240302
0.8571	High Similarity	NPC170038
0.8571	High Similarity	NPC294266
0.8571	High Similarity	NPC56525
0.8556	High Similarity	NPC218301
0.8542	High Similarity	NPC164835
0.8542	High Similarity	NPC228669
0.8539	High Similarity	NPC305039
0.8539	High Similarity	NPC54689
0.8539	High Similarity	NPC474570
0.8495	Intermediate Similarity	NPC57416
0.8495	Intermediate Similarity	NPC107243
0.8495	Intermediate Similarity	NPC187159
0.8488	Intermediate Similarity	NPC470046
0.8488	Intermediate Similarity	NPC470047
0.8471	Intermediate Similarity	NPC147066
0.8471	Intermediate Similarity	NPC474955
0.8462	Intermediate Similarity	NPC66429
0.8462	Intermediate Similarity	NPC470376
0.8462	Intermediate Similarity	NPC152897
0.8462	Intermediate Similarity	NPC470375
0.8462	Intermediate Similarity	NPC475700
0.8452	Intermediate Similarity	NPC118987
0.8452	Intermediate Similarity	NPC44083
0.8452	Intermediate Similarity	NPC153987
0.8444	Intermediate Similarity	NPC471896
0.8427	Intermediate Similarity	NPC294480
0.8421	Intermediate Similarity	NPC474327
0.8409	Intermediate Similarity	NPC155011
0.8409	Intermediate Similarity	NPC469994
0.8404	Intermediate Similarity	NPC176845
0.8391	Intermediate Similarity	NPC109512
0.8372	Intermediate Similarity	NPC100297
0.837	Intermediate Similarity	NPC159410
0.8367	Intermediate Similarity	NPC220974
0.8351	Intermediate Similarity	NPC472228
0.8351	Intermediate Similarity	NPC472227
0.8333	Intermediate Similarity	NPC476733
0.8333	Intermediate Similarity	NPC477943
0.8333	Intermediate Similarity	NPC215029
0.8333	Intermediate Similarity	NPC35574
0.8333	Intermediate Similarity	NPC474679
0.8316	Intermediate Similarity	NPC218383
0.8315	Intermediate Similarity	NPC312215
0.8315	Intermediate Similarity	NPC474684
0.8315	Intermediate Similarity	NPC142361
0.8315	Intermediate Similarity	NPC317590
0.8315	Intermediate Similarity	NPC96496
0.8298	Intermediate Similarity	NPC292133
0.828	Intermediate Similarity	NPC184848
0.828	Intermediate Similarity	NPC280877
0.828	Intermediate Similarity	NPC69548
0.828	Intermediate Similarity	NPC263347
0.8276	Intermediate Similarity	NPC170862
0.8261	Intermediate Similarity	NPC170220
0.8261	Intermediate Similarity	NPC141497
0.8261	Intermediate Similarity	NPC243866
0.8261	Intermediate Similarity	NPC107674
0.8256	Intermediate Similarity	NPC475665
0.8256	Intermediate Similarity	NPC201912
0.8256	Intermediate Similarity	NPC38350
0.8242	Intermediate Similarity	NPC175628
0.8242	Intermediate Similarity	NPC148414
0.8242	Intermediate Similarity	NPC111585
0.8242	Intermediate Similarity	NPC171441
0.8235	Intermediate Similarity	NPC477371
0.8235	Intermediate Similarity	NPC471475
0.8222	Intermediate Similarity	NPC328313
0.8222	Intermediate Similarity	NPC183546
0.8214	Intermediate Similarity	NPC472300
0.8211	Intermediate Similarity	NPC477813
0.8211	Intermediate Similarity	NPC252295
0.8202	Intermediate Similarity	NPC212843
0.8191	Intermediate Similarity	NPC155676
0.8191	Intermediate Similarity	NPC307164
0.8191	Intermediate Similarity	NPC58052
0.8191	Intermediate Similarity	NPC42042
0.8191	Intermediate Similarity	NPC111684
0.8182	Intermediate Similarity	NPC165064
0.8182	Intermediate Similarity	NPC214043
0.8182	Intermediate Similarity	NPC221758
0.8182	Intermediate Similarity	NPC321187
0.8182	Intermediate Similarity	NPC329043
0.8182	Intermediate Similarity	NPC85774
0.8182	Intermediate Similarity	NPC58841
0.8182	Intermediate Similarity	NPC312660
0.8182	Intermediate Similarity	NPC59453
0.8182	Intermediate Similarity	NPC161423
0.8182	Intermediate Similarity	NPC227064
0.8163	Intermediate Similarity	NPC255309
0.8161	Intermediate Similarity	NPC321289
0.8161	Intermediate Similarity	NPC260956
0.8161	Intermediate Similarity	NPC327969
0.8161	Intermediate Similarity	NPC133391
0.8161	Intermediate Similarity	NPC320514
0.8152	Intermediate Similarity	NPC110657
0.8152	Intermediate Similarity	NPC297265
0.8152	Intermediate Similarity	NPC26888
0.8152	Intermediate Similarity	NPC190442
0.8152	Intermediate Similarity	NPC212301
0.8152	Intermediate Similarity	NPC86266
0.8152	Intermediate Similarity	NPC23434
0.8144	Intermediate Similarity	NPC308351
0.8144	Intermediate Similarity	NPC473928
0.8144	Intermediate Similarity	NPC271266
0.8144	Intermediate Similarity	NPC22388
0.814	Intermediate Similarity	NPC267517
0.8132	Intermediate Similarity	NPC2983
0.8132	Intermediate Similarity	NPC474889
0.8132	Intermediate Similarity	NPC76879
0.8132	Intermediate Similarity	NPC475921
0.8132	Intermediate Similarity	NPC474704
0.8125	Intermediate Similarity	NPC128698
0.8125	Intermediate Similarity	NPC239768
0.8118	Intermediate Similarity	NPC63020
0.8118	Intermediate Similarity	NPC4827
0.8111	Intermediate Similarity	NPC159046
0.8111	Intermediate Similarity	NPC233836
0.8111	Intermediate Similarity	NPC187376
0.8105	Intermediate Similarity	NPC23680
0.8095	Intermediate Similarity	NPC41017
0.809	Intermediate Similarity	NPC470048
0.809	Intermediate Similarity	NPC29447
0.809	Intermediate Similarity	NPC471224
0.8085	Intermediate Similarity	NPC222845
0.8085	Intermediate Similarity	NPC162001
0.8085	Intermediate Similarity	NPC45324
0.8081	Intermediate Similarity	NPC196528
0.8081	Intermediate Similarity	NPC96377
0.8072	Intermediate Similarity	NPC166797
0.8068	Intermediate Similarity	NPC83569
0.8068	Intermediate Similarity	NPC477852
0.8068	Intermediate Similarity	NPC245866
0.8068	Intermediate Similarity	NPC69279
0.8065	Intermediate Similarity	NPC49776
0.8065	Intermediate Similarity	NPC206810
0.8065	Intermediate Similarity	NPC472226
0.8065	Intermediate Similarity	NPC474436
0.8065	Intermediate Similarity	NPC63118
0.8065	Intermediate Similarity	NPC472225
0.8065	Intermediate Similarity	NPC229976
0.8061	Intermediate Similarity	NPC36688
0.8046	Intermediate Similarity	NPC477372
0.8046	Intermediate Similarity	NPC232625
0.8043	Intermediate Similarity	NPC475965
0.8043	Intermediate Similarity	NPC123854
0.8043	Intermediate Similarity	NPC320026
0.8043	Intermediate Similarity	NPC474842
0.8043	Intermediate Similarity	NPC46281
0.8043	Intermediate Similarity	NPC44240
0.8041	Intermediate Similarity	NPC99411
0.8022	Intermediate Similarity	NPC247406
0.8022	Intermediate Similarity	NPC470612
0.8022	Intermediate Similarity	NPC470613
0.8022	Intermediate Similarity	NPC48866
0.8022	Intermediate Similarity	NPC226863
0.8	Intermediate Similarity	NPC471042
0.8	Intermediate Similarity	NPC474732
0.8	Intermediate Similarity	NPC51014
0.8	Intermediate Similarity	NPC286153
0.8	Intermediate Similarity	NPC474778
0.8	Intermediate Similarity	NPC91525
0.8	Intermediate Similarity	NPC55309
0.8	Intermediate Similarity	NPC472505
0.8	Intermediate Similarity	NPC80590
0.8	Intermediate Similarity	NPC325594
0.8	Intermediate Similarity	NPC28252
0.8	Intermediate Similarity	NPC329943
0.8	Intermediate Similarity	NPC31564
0.8	Intermediate Similarity	NPC474733
0.8	Intermediate Similarity	NPC9892
0.8	Intermediate Similarity	NPC10005
0.8	Intermediate Similarity	NPC145879
0.798	Intermediate Similarity	NPC471293
0.798	Intermediate Similarity	NPC119329

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 NPC28227 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	180
0.1-0.2	1573
0.2-0.3	4380
0.3-0.4	2059
0.4-0.5	494
0.5-0.6	160
0.6-0.7	155
0.7-0.8	119
0.8-0.85	18
0.85-0.9	5
0.9-0.95	6
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9294	High Similarity	NPD6903	Approved
0.9286	High Similarity	NPD7146	Approved
0.9286	High Similarity	NPD6409	Approved
0.9286	High Similarity	NPD7334	Approved
0.9286	High Similarity	NPD6684	Approved
0.9286	High Similarity	NPD5330	Approved
0.9286	High Similarity	NPD7521	Approved
0.907	High Similarity	NPD7513	Clinical (unspecified phase)
0.8889	High Similarity	NPD6356	Clinical (unspecified phase)
0.8837	High Similarity	NPD6098	Approved
0.8667	High Similarity	NPD6399	Phase 3
0.8652	High Similarity	NPD5207	Approved
0.8636	High Similarity	NPD5737	Approved
0.8636	High Similarity	NPD6672	Approved
0.8571	High Similarity	NPD6001	Approved
0.8539	High Similarity	NPD6904	Approved
0.8539	High Similarity	NPD6080	Approved
0.8539	High Similarity	NPD6673	Approved
0.8427	Intermediate Similarity	NPD5208	Approved
0.8298	Intermediate Similarity	NPD6083	Phase 2
0.8298	Intermediate Similarity	NPD6084	Phase 2
0.8265	Intermediate Similarity	NPD6008	Approved
0.8211	Intermediate Similarity	NPD5696	Approved
0.8182	Intermediate Similarity	NPD3133	Approved
0.8182	Intermediate Similarity	NPD3666	Approved
0.8182	Intermediate Similarity	NPD3665	Phase 1
0.8182	Intermediate Similarity	NPD4786	Approved
0.8152	Intermediate Similarity	NPD5693	Phase 1
0.8152	Intermediate Similarity	NPD6050	Approved
0.8085	Intermediate Similarity	NPD5695	Phase 3
0.8061	Intermediate Similarity	NPD6052	Approved
0.8043	Intermediate Similarity	NPD5692	Phase 3
0.7957	Intermediate Similarity	NPD5694	Approved
0.7955	Intermediate Similarity	NPD4223	Phase 3
0.7955	Intermediate Similarity	NPD4221	Approved
0.7955	Intermediate Similarity	NPD3667	Approved
0.7935	Intermediate Similarity	NPD6051	Approved
0.7921	Intermediate Similarity	NPD7320	Approved
0.79	Intermediate Similarity	NPD7128	Approved
0.79	Intermediate Similarity	NPD6675	Approved
0.79	Intermediate Similarity	NPD5739	Approved
0.79	Intermediate Similarity	NPD6402	Approved
0.7889	Intermediate Similarity	NPD5329	Approved
0.7843	Intermediate Similarity	NPD6373	Approved
0.7843	Intermediate Similarity	NPD6372	Approved
0.7831	Intermediate Similarity	NPD5777	Approved
0.7802	Intermediate Similarity	NPD3618	Phase 1
0.7789	Intermediate Similarity	NPD7900	Approved
0.7789	Intermediate Similarity	NPD7901	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD4197	Approved
0.7778	Intermediate Similarity	NPD3668	Phase 3
0.7766	Intermediate Similarity	NPD5284	Approved
0.7766	Intermediate Similarity	NPD5281	Approved
0.7745	Intermediate Similarity	NPD6881	Approved
0.7745	Intermediate Similarity	NPD6899	Approved
0.7742	Intermediate Similarity	NPD4753	Phase 2
0.7742	Intermediate Similarity	NPD5328	Approved
0.7692	Intermediate Similarity	NPD6649	Approved
0.7692	Intermediate Similarity	NPD6650	Approved
0.7684	Intermediate Similarity	NPD4202	Approved
0.7647	Intermediate Similarity	NPD5697	Approved
0.7647	Intermediate Similarity	NPD5701	Approved
0.7609	Intermediate Similarity	NPD4138	Approved
0.7609	Intermediate Similarity	NPD4688	Approved
0.7609	Intermediate Similarity	NPD4693	Phase 3
0.7609	Intermediate Similarity	NPD4690	Approved
0.7609	Intermediate Similarity	NPD4689	Approved
0.7609	Intermediate Similarity	NPD5205	Approved
0.7604	Intermediate Similarity	NPD7748	Approved
0.7596	Intermediate Similarity	NPD7290	Approved
0.7596	Intermediate Similarity	NPD7102	Approved
0.7596	Intermediate Similarity	NPD6883	Approved
0.7579	Intermediate Similarity	NPD6079	Approved
0.7579	Intermediate Similarity	NPD8034	Phase 2
0.7579	Intermediate Similarity	NPD8035	Phase 2
0.7573	Intermediate Similarity	NPD6011	Approved
0.7551	Intermediate Similarity	NPD7902	Approved
0.7526	Intermediate Similarity	NPD5210	Approved
0.7526	Intermediate Similarity	NPD4629	Approved
0.7526	Intermediate Similarity	NPD5654	Approved
0.7524	Intermediate Similarity	NPD8130	Phase 1
0.7524	Intermediate Similarity	NPD6617	Approved
0.7524	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.7524	Intermediate Similarity	NPD6869	Approved
0.7524	Intermediate Similarity	NPD6847	Approved
0.75	Intermediate Similarity	NPD4747	Approved
0.75	Intermediate Similarity	NPD7520	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD6012	Approved
0.75	Intermediate Similarity	NPD6014	Approved
0.75	Intermediate Similarity	NPD1694	Approved
0.75	Intermediate Similarity	NPD6013	Approved
0.7476	Intermediate Similarity	NPD6614	Approved
0.7473	Intermediate Similarity	NPD4788	Approved
0.7453	Intermediate Similarity	NPD8297	Approved
0.7453	Intermediate Similarity	NPD6882	Approved
0.7419	Intermediate Similarity	NPD5690	Phase 2
0.7419	Intermediate Similarity	NPD5280	Approved
0.7419	Intermediate Similarity	NPD5279	Phase 3
0.7419	Intermediate Similarity	NPD4694	Approved
0.7396	Intermediate Similarity	NPD7515	Phase 2
0.7381	Intermediate Similarity	NPD4137	Phase 3
0.7374	Intermediate Similarity	NPD4755	Approved
0.7374	Intermediate Similarity	NPD5959	Approved
0.7363	Intermediate Similarity	NPD4752	Clinical (unspecified phase)
0.734	Intermediate Similarity	NPD3573	Approved
0.7308	Intermediate Similarity	NPD6412	Phase 2
0.73	Intermediate Similarity	NPD7638	Approved
0.7294	Intermediate Similarity	NPD4691	Approved
0.7273	Intermediate Similarity	NPD3701	Clinical (unspecified phase)
0.7273	Intermediate Similarity	NPD4697	Phase 3
0.7262	Intermediate Similarity	NPD3621	Clinical (unspecified phase)
0.7253	Intermediate Similarity	NPD4139	Approved
0.7253	Intermediate Similarity	NPD4692	Approved
0.7241	Intermediate Similarity	NPD5733	Approved
0.7234	Intermediate Similarity	NPD3574	Clinical (unspecified phase)
0.7232	Intermediate Similarity	NPD6291	Clinical (unspecified phase)
0.7228	Intermediate Similarity	NPD5286	Approved
0.7228	Intermediate Similarity	NPD4700	Approved
0.7228	Intermediate Similarity	NPD4696	Approved
0.7228	Intermediate Similarity	NPD7639	Approved
0.7228	Intermediate Similarity	NPD7640	Approved
0.7228	Intermediate Similarity	NPD5285	Approved
0.7222	Intermediate Similarity	NPD7094	Approved
0.7222	Intermediate Similarity	NPD6858	Approved
0.7222	Intermediate Similarity	NPD4195	Approved
0.7209	Intermediate Similarity	NPD4243	Approved
0.7159	Intermediate Similarity	NPD7339	Approved
0.7159	Intermediate Similarity	NPD3702	Approved
0.7159	Intermediate Similarity	NPD6942	Approved
0.7157	Intermediate Similarity	NPD5223	Approved
0.7117	Intermediate Similarity	NPD6335	Approved
0.7111	Intermediate Similarity	NPD3617	Approved
0.71	Intermediate Similarity	NPD5222	Approved
0.71	Intermediate Similarity	NPD5220	Clinical (unspecified phase)
0.71	Intermediate Similarity	NPD5349	Clinical (unspecified phase)
0.71	Intermediate Similarity	NPD5221	Approved
0.7097	Intermediate Similarity	NPD5362	Discontinued
0.7091	Intermediate Similarity	NPD6274	Approved
0.7087	Intermediate Similarity	NPD5211	Phase 2
0.7087	Intermediate Similarity	NPD5226	Approved
0.7087	Intermediate Similarity	NPD5224	Approved
0.7087	Intermediate Similarity	NPD4633	Approved
0.7087	Intermediate Similarity	NPD5225	Approved
0.7065	Intermediate Similarity	NPD5369	Approved
0.7064	Intermediate Similarity	NPD4632	Approved
0.7054	Intermediate Similarity	NPD7100	Approved
0.7054	Intermediate Similarity	NPD7101	Approved
0.7045	Intermediate Similarity	NPD4785	Approved
0.7045	Intermediate Similarity	NPD4784	Approved
0.7045	Intermediate Similarity	NPD4058	Approved
0.7045	Intermediate Similarity	NPD4687	Approved
0.7043	Intermediate Similarity	NPD7492	Approved
0.703	Intermediate Similarity	NPD5173	Approved
0.7027	Intermediate Similarity	NPD6317	Approved
0.7027	Intermediate Similarity	NPD7115	Discovery
0.7019	Intermediate Similarity	NPD5175	Approved
0.7019	Intermediate Similarity	NPD4754	Approved
0.7019	Intermediate Similarity	NPD5174	Approved
0.7011	Intermediate Similarity	NPD5276	Approved
0.6991	Remote Similarity	NPD6059	Approved
0.6991	Remote Similarity	NPD6054	Approved
0.6989	Remote Similarity	NPD6435	Approved
0.6983	Remote Similarity	NPD6616	Approved
0.6964	Remote Similarity	NPD6313	Approved
0.6964	Remote Similarity	NPD6314	Approved
0.6952	Remote Similarity	NPD5141	Approved
0.6939	Remote Similarity	NPD4096	Approved
0.6937	Remote Similarity	NPD6868	Approved
0.693	Remote Similarity	NPD6909	Approved
0.693	Remote Similarity	NPD6908	Approved
0.6923	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6923	Remote Similarity	NPD8293	Discontinued
0.6923	Remote Similarity	NPD7078	Approved
0.69	Remote Similarity	NPD5707	Approved
0.6897	Remote Similarity	NPD4244	Approved
0.6897	Remote Similarity	NPD4245	Approved
0.6887	Remote Similarity	NPD4768	Approved
0.6887	Remote Similarity	NPD4767	Approved
0.6875	Remote Similarity	NPD6009	Approved
0.687	Remote Similarity	NPD6370	Approved
0.6869	Remote Similarity	NPD6411	Approved
0.6864	Remote Similarity	NPD7736	Approved
0.6854	Remote Similarity	NPD6113	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD6319	Approved
0.6837	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.6818	Remote Similarity	NPD6053	Discontinued
0.681	Remote Similarity	NPD7604	Phase 2
0.6809	Remote Similarity	NPD4269	Approved
0.6809	Remote Similarity	NPD4270	Approved
0.68	Remote Similarity	NPD5133	Approved
0.6783	Remote Similarity	NPD5983	Phase 2
0.6783	Remote Similarity	NPD6015	Approved
0.6783	Remote Similarity	NPD6016	Approved
0.6782	Remote Similarity	NPD3698	Phase 2
0.6778	Remote Similarity	NPD8039	Approved
0.6778	Remote Similarity	NPD4190	Phase 3
0.6778	Remote Similarity	NPD5275	Approved
0.6774	Remote Similarity	NPD5368	Approved
0.6774	Remote Similarity	NPD7525	Registered
0.6774	Remote Similarity	NPD4695	Discontinued

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