NPASS Compound

Structure

CID72796 OpenBabel06191715412D 32 34 0 0 1 0 0 0 0 0999 V2000 1.3975 -5.5328 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7859 -4.8126 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9641 -1.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0981 -6.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0428 -5.4817 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8301 -4.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2601 -1.2601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -2.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7248 -2.9074 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4190 -2.5472 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2321 -2.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3660 -4.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4680 -2.2382 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3660 -3.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3090 -0.9511 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5000 -1.5388 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9328 -3.8855 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6270 -3.5254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0981 -3.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2321 -4.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8838 -4.1945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0981 -4.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 -0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2601 -1.2601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1896 -4.5546 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5780 -3.8344 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9641 -2.5388 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2321 -5.5388 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0917 -5.1727 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9641 -4.5388 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 26 1 0 0 0 0 2 27 1 0 0 0 0 3 28 1 0 0 0 0 4 29 1 0 0 0 0 5 30 1 0 0 0 0 6 31 1 0 0 0 0 7 14 1 0 0 0 0 8 15 1 0 0 0 0 9 14 2 0 0 0 0 9 18 1 0 0 0 0 10 14 1 0 0 0 0 10 19 2 0 0 0 0 11 15 2 0 0 0 0 11 20 1 0 0 0 0 12 15 1 0 0 0 0 12 21 2 0 0 0 0 13 16 1 0 0 0 0 13 32 1 0 0 0 0 16 7 1 6 0 0 0 16 17 1 0 0 0 0 17 8 1 1 0 0 0 17 24 1 0 0 0 0 18 22 2 0 0 0 0 18 26 1 0 0 0 0 19 22 1 0 0 0 0 19 27 1 0 0 0 0 20 23 2 0 0 0 0 20 28 1 0 0 0 0 21 23 1 0 0 0 0 21 29 1 0 0 0 0 22 30 1 0 0 0 0 23 31 1 0 0 0 0 24 25 2 0 0 0 0 24 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	446.19
Volume:	449.857
LogP:	2.823
LogD:	3.131
LogS:	-4.149
# Rotatable Bonds:	10
TPSA:	81.68
# H-Bond Aceptor:	8
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.514
Synthetic Accessibility Score:	3.217
Fsp3:	0.458
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:	-4.772
MDCK Permeability:	3.8992537156445906e-05
Pgp-inhibitor:	0.999
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.321

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.086
Plasma Protein Binding (PPB):	73.13738250732422%
Volume Distribution (VD):	0.623
Pgp-substrate:	18.75535774230957%

ADMET: Metabolism

CYP1A2-inhibitor:	0.088
CYP1A2-substrate:	0.898
CYP2C19-inhibitor:	0.49
CYP2C19-substrate:	0.936
CYP2C9-inhibitor:	0.501
CYP2C9-substrate:	0.748
CYP2D6-inhibitor:	0.021
CYP2D6-substrate:	0.922
CYP3A4-inhibitor:	0.944
CYP3A4-substrate:	0.921

ADMET: Excretion

Clearance (CL):	8.673
Half-life (T1/2):	0.74

ADMET: Toxicity

hERG Blockers:	0.284
Human Hepatotoxicity (H-HT):	0.12
Drug-inuced Liver Injury (DILI):	0.803
AMES Toxicity:	0.068
Rat Oral Acute Toxicity:	0.031
Maximum Recommended Daily Dose:	0.128
Skin Sensitization:	0.924
Carcinogencity:	0.03
Eye Corrosion:	0.003
Eye Irritation:	0.065
Respiratory Toxicity:	0.198

Download Data

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

Natural Product: NPC72796

Natural Product ID:	NPC72796
*Common Name:**	(-)-Cubebininolide
IUPAC Name:	(3R,4R)-3,4-bis[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one
Synonyms:	(-)-Cubebininolide
Standard InCHIKey:	VUNCHONBJWJYID-DLBZAZTESA-N
Standard InCHI:	InChI=1S/C24H30O8/c1-26-18-9-14(10-19(27-2)22(18)30-5)7-16-13-32-24(25)17(16)8-15-11-20(28-3)23(31-6)21(12-15)29-4/h9-12,16-17H,7-8,13H2,1-6H3/t16-,17+/m0/s1
SMILES:	COc1c(OC)cc(cc1OC)C[C@H]1C(=O)OC[C@@H]1Cc1cc(OC)c(c(c1)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL479314
PubChem CID:	13916150
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003424] 9,9'-epoxylignans [CHEMONTID:0001613] Dibenzylbutyrolactone lignans

*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
NPO11169	Piper cubeba	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15679319]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	n.a.	fruit	n.a.	PMID[22396124]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23501116]
NPO11169	Piper cubeba	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO11169	Piper cubeba	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO11169	Piper cubeba	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11169	Piper cubeba	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10449	Arctium lappa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10449	Arctium lappa	Species	Asteraceae	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	2

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT109	Individual Protein	Cytochrome P450 3A4	Homo sapiens	IC50	=	14900.0	nM	PMID[464852]
NPT110	Individual Protein	Cytochrome P450 2D6	Homo sapiens	IC50	>	100000.0	nM	PMID[464852]

☑ 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 NPC72796 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	344
0.1-0.2	1364
0.2-0.3	3048
0.3-0.4	8148
0.4-0.5	10994
0.5-0.6	3956
0.6-0.7	9116
0.7-0.8	5230
0.8-0.85	341
0.85-0.9	114
0.9-0.95	37
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC44245
0.9845	High Similarity	NPC211386
0.9552	High Similarity	NPC40237
0.9552	High Similarity	NPC151423
0.9481	High Similarity	NPC477696
0.9481	High Similarity	NPC477697
0.9481	High Similarity	NPC470811
0.9412	High Similarity	NPC92693
0.9412	High Similarity	NPC475000
0.9412	High Similarity	NPC218841
0.9407	High Similarity	NPC210354
0.9407	High Similarity	NPC176586
0.9338	High Similarity	NPC273657
0.9338	High Similarity	NPC106920
0.9275	High Similarity	NPC193779
0.927	High Similarity	NPC191158
0.927	High Similarity	NPC177644
0.927	High Similarity	NPC18211
0.927	High Similarity	NPC143092
0.9225	High Similarity	NPC223807
0.9197	High Similarity	NPC474288
0.9179	High Similarity	NPC209229
0.9078	High Similarity	NPC474965
0.9078	High Similarity	NPC668
0.9078	High Similarity	NPC293757
0.9078	High Similarity	NPC477698
0.9078	High Similarity	NPC174512
0.9078	High Similarity	NPC477695
0.9078	High Similarity	NPC125570
0.9071	High Similarity	NPC104024
0.9071	High Similarity	NPC65574
0.9071	High Similarity	NPC80230
0.9071	High Similarity	NPC304687
0.9071	High Similarity	NPC101755
0.9037	High Similarity	NPC143895
0.9037	High Similarity	NPC11453
0.9014	High Similarity	NPC149505
0.8951	High Similarity	NPC210642
0.8951	High Similarity	NPC477700
0.8951	High Similarity	NPC303519
0.8951	High Similarity	NPC13985
0.8951	High Similarity	NPC164082
0.8944	High Similarity	NPC145569
0.8944	High Similarity	NPC177476
0.8944	High Similarity	NPC216223
0.8944	High Similarity	NPC262455
0.8929	High Similarity	NPC474158
0.8889	High Similarity	NPC477699
0.8889	High Similarity	NPC476434
0.8889	High Similarity	NPC56184
0.8873	High Similarity	NPC40654
0.8873	High Similarity	NPC262804
0.8865	High Similarity	NPC213482
0.8864	High Similarity	NPC328682
0.8864	High Similarity	NPC281864
0.8864	High Similarity	NPC54321
0.8855	High Similarity	NPC186845
0.8855	High Similarity	NPC285725
0.8855	High Similarity	NPC112571
0.8855	High Similarity	NPC88297
0.8855	High Similarity	NPC9891
0.8855	High Similarity	NPC50683
0.8849	High Similarity	NPC253722
0.8849	High Similarity	NPC253481
0.8849	High Similarity	NPC46180
0.8849	High Similarity	NPC31751
0.8828	High Similarity	NPC178574
0.8828	High Similarity	NPC473236
0.8828	High Similarity	NPC65591
0.8819	High Similarity	NPC32079
0.8815	High Similarity	NPC205915
0.8788	High Similarity	NPC8050
0.8788	High Similarity	NPC473093
0.8788	High Similarity	NPC473092
0.8779	High Similarity	NPC173608
0.8777	High Similarity	NPC100675
0.8767	High Similarity	NPC348849
0.8767	High Similarity	NPC178195
0.8767	High Similarity	NPC136757
0.8767	High Similarity	NPC273578
0.875	High Similarity	NPC300776
0.875	High Similarity	NPC5310
0.875	High Similarity	NPC4982
0.875	High Similarity	NPC68779
0.875	High Similarity	NPC176814
0.8732	High Similarity	NPC321696
0.8732	High Similarity	NPC321958
0.8731	High Similarity	NPC79184
0.8731	High Similarity	NPC307042
0.8723	High Similarity	NPC27159
0.8722	High Similarity	NPC210674
0.8722	High Similarity	NPC222127
0.8722	High Similarity	NPC82862
0.8714	High Similarity	NPC287124
0.8699	High Similarity	NPC245948
0.8696	High Similarity	NPC865
0.8676	High Similarity	NPC1474
0.8667	High Similarity	NPC192255
0.8662	High Similarity	NPC223185
0.8662	High Similarity	NPC318286
0.8662	High Similarity	NPC327651
0.8652	High Similarity	NPC218510
0.8652	High Similarity	NPC76415
0.8649	High Similarity	NPC32373
0.8649	High Similarity	NPC237946
0.8643	High Similarity	NPC470991
0.8639	High Similarity	NPC30009
0.8639	High Similarity	NPC103197
0.8623	High Similarity	NPC471182
0.8615	High Similarity	NPC477886
0.8613	High Similarity	NPC37065
0.8613	High Similarity	NPC110958
0.8613	High Similarity	NPC19890
0.8613	High Similarity	NPC145769
0.8611	High Similarity	NPC304821
0.8603	High Similarity	NPC65183
0.8603	High Similarity	NPC72046
0.8603	High Similarity	NPC261812
0.8593	High Similarity	NPC237169
0.8593	High Similarity	NPC476399
0.8593	High Similarity	NPC470624
0.8592	High Similarity	NPC326144
0.8592	High Similarity	NPC477701
0.8592	High Similarity	NPC166884
0.8592	High Similarity	NPC141569
0.8591	High Similarity	NPC163527
0.8591	High Similarity	NPC115281
0.8591	High Similarity	NPC207584
0.8591	High Similarity	NPC19947
0.8591	High Similarity	NPC181168
0.8582	High Similarity	NPC474623
0.8582	High Similarity	NPC474651
0.8571	High Similarity	NPC474514
0.8562	High Similarity	NPC474975
0.8562	High Similarity	NPC62354
0.8561	High Similarity	NPC281780
0.8551	High Similarity	NPC311430
0.8551	High Similarity	NPC236522
0.8551	High Similarity	NPC148893
0.8551	High Similarity	NPC113295
0.8551	High Similarity	NPC25333
0.8551	High Similarity	NPC49235
0.8551	High Similarity	NPC224941
0.854	High Similarity	NPC266848
0.854	High Similarity	NPC288743
0.854	High Similarity	NPC136750
0.8533	High Similarity	NPC325122
0.8531	High Similarity	NPC477702
0.8527	High Similarity	NPC475961
0.8527	High Similarity	NPC254625
0.8523	High Similarity	NPC477380
0.8521	High Similarity	NPC474966
0.8519	High Similarity	NPC153547
0.85	High Similarity	NPC470962
0.8493	Intermediate Similarity	NPC316989
0.8493	Intermediate Similarity	NPC158635
0.8493	Intermediate Similarity	NPC229882
0.8489	Intermediate Similarity	NPC90431
0.8489	Intermediate Similarity	NPC121651
0.8489	Intermediate Similarity	NPC471988
0.8483	Intermediate Similarity	NPC327352
0.8483	Intermediate Similarity	NPC252281
0.8483	Intermediate Similarity	NPC477375
0.8483	Intermediate Similarity	NPC198129
0.8478	Intermediate Similarity	NPC244983
0.8478	Intermediate Similarity	NPC309744
0.8478	Intermediate Similarity	NPC31530
0.8478	Intermediate Similarity	NPC67247
0.8478	Intermediate Similarity	NPC326095
0.8477	Intermediate Similarity	NPC91634
0.8477	Intermediate Similarity	NPC96593
0.8477	Intermediate Similarity	NPC268718
0.8477	Intermediate Similarity	NPC150943
0.8477	Intermediate Similarity	NPC119910
0.8473	Intermediate Similarity	NPC65933
0.8473	Intermediate Similarity	NPC172676
0.8473	Intermediate Similarity	NPC312713
0.8473	Intermediate Similarity	NPC126935
0.8473	Intermediate Similarity	NPC216929
0.8473	Intermediate Similarity	NPC57268
0.8472	Intermediate Similarity	NPC87295
0.8472	Intermediate Similarity	NPC3982
0.8472	Intermediate Similarity	NPC212890
0.8467	Intermediate Similarity	NPC475856
0.8467	Intermediate Similarity	NPC204215
0.8467	Intermediate Similarity	NPC477885
0.8467	Intermediate Similarity	NPC175067
0.8462	Intermediate Similarity	NPC474036
0.8456	Intermediate Similarity	NPC234730
0.8456	Intermediate Similarity	NPC238834
0.8451	Intermediate Similarity	NPC52664
0.8446	Intermediate Similarity	NPC475116
0.844	Intermediate Similarity	NPC147379
0.844	Intermediate Similarity	NPC203351
0.8429	Intermediate Similarity	NPC283949
0.8425	Intermediate Similarity	NPC477376
0.8425	Intermediate Similarity	NPC322426
0.8425	Intermediate Similarity	NPC477374
0.8425	Intermediate Similarity	NPC85141
0.8421	Intermediate Similarity	NPC121783

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 NPC72796 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	279
0.1-0.2	853
0.2-0.3	1612
0.3-0.4	2653
0.4-0.5	1936
0.5-0.6	1152
0.6-0.7	529
0.7-0.8	128
0.8-0.85	4
0.85-0.9	4
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8699	High Similarity	NPD37	Approved
0.8649	High Similarity	NPD4966	Approved
0.8649	High Similarity	NPD4967	Phase 2
0.8649	High Similarity	NPD4965	Approved
0.8533	High Similarity	NPD6234	Discontinued
0.8483	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.8301	Intermediate Similarity	NPD7199	Phase 2
0.8194	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.8153	Intermediate Similarity	NPD7228	Approved
0.8062	Intermediate Similarity	NPD5283	Phase 1
0.8058	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.8027	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.8	Intermediate Similarity	NPD5494	Approved
0.8	Intermediate Similarity	NPD2981	Phase 2
0.7986	Intermediate Similarity	NPD3027	Phase 3
0.7974	Intermediate Similarity	NPD3817	Phase 2
0.795	Intermediate Similarity	NPD7240	Approved
0.7945	Intermediate Similarity	NPD4110	Phase 3
0.7945	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7941	Intermediate Similarity	NPD2983	Phase 2
0.7941	Intermediate Similarity	NPD2982	Phase 2
0.7926	Intermediate Similarity	NPD3705	Approved
0.7922	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7917	Intermediate Similarity	NPD2438	Suspended
0.791	Intermediate Similarity	NPD17	Approved
0.7848	Intermediate Similarity	NPD5242	Approved
0.7842	Intermediate Similarity	NPD3018	Phase 2
0.7806	Intermediate Similarity	NPD3882	Suspended
0.7785	Intermediate Similarity	NPD6232	Discontinued
0.7762	Intermediate Similarity	NPD6355	Discontinued
0.775	Intermediate Similarity	NPD7473	Discontinued
0.7742	Intermediate Similarity	NPD5353	Approved
0.7737	Intermediate Similarity	NPD1608	Approved
0.7736	Intermediate Similarity	NPD3926	Phase 2
0.7707	Intermediate Similarity	NPD919	Approved
0.7697	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7692	Intermediate Similarity	NPD2979	Phase 3
0.7687	Intermediate Similarity	NPD5536	Phase 2
0.7664	Intermediate Similarity	NPD1281	Approved
0.7639	Intermediate Similarity	NPD230	Phase 1
0.7613	Intermediate Similarity	NPD1934	Approved
0.7603	Intermediate Similarity	NPD3748	Approved
0.7593	Intermediate Similarity	NPD3818	Discontinued
0.7574	Intermediate Similarity	NPD5585	Approved
0.7568	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7564	Intermediate Similarity	NPD1465	Phase 2
0.7564	Intermediate Similarity	NPD2801	Approved
0.7564	Intermediate Similarity	NPD7819	Suspended
0.7562	Intermediate Similarity	NPD7229	Phase 3
0.755	Intermediate Similarity	NPD6799	Approved
0.7548	Intermediate Similarity	NPD6385	Approved
0.7548	Intermediate Similarity	NPD6386	Approved
0.7546	Intermediate Similarity	NPD5844	Phase 1
0.7533	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD2532	Approved
0.75	Intermediate Similarity	NPD2534	Approved
0.75	Intermediate Similarity	NPD1283	Approved
0.75	Intermediate Similarity	NPD2533	Approved
0.7484	Intermediate Similarity	NPD6599	Discontinued
0.7467	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7467	Intermediate Similarity	NPD4628	Phase 3
0.7465	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7452	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7451	Intermediate Similarity	NPD1940	Clinical (unspecified phase)
0.7448	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7448	Intermediate Similarity	NPD1613	Approved
0.7445	Intermediate Similarity	NPD1651	Approved
0.744	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7434	Intermediate Similarity	NPD4357	Discontinued
0.7432	Intermediate Similarity	NPD2531	Phase 2
0.7432	Intermediate Similarity	NPD2796	Approved
0.7431	Intermediate Similarity	NPD6798	Discontinued
0.7419	Intermediate Similarity	NPD6055	Clinical (unspecified phase)
0.7417	Intermediate Similarity	NPD6190	Approved
0.7413	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7413	Intermediate Similarity	NPD4908	Phase 1
0.7391	Intermediate Similarity	NPD1247	Approved
0.7391	Intermediate Similarity	NPD8127	Discontinued
0.7386	Intermediate Similarity	NPD3146	Approved
0.7386	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.7386	Intermediate Similarity	NPD3688	Clinical (unspecified phase)
0.7379	Intermediate Similarity	NPD8032	Phase 2
0.7379	Intermediate Similarity	NPD6233	Phase 2
0.7368	Intermediate Similarity	NPD7124	Phase 2
0.7362	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7362	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7362	Intermediate Similarity	NPD6166	Phase 2
0.7361	Intermediate Similarity	NPD7095	Approved
0.7351	Intermediate Similarity	NPD3750	Approved
0.7349	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.7342	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7329	Intermediate Similarity	NPD4060	Phase 1
0.7325	Intermediate Similarity	NPD7615	Clinical (unspecified phase)
0.7324	Intermediate Similarity	NPD3267	Approved
0.7324	Intermediate Similarity	NPD3266	Approved
0.7324	Intermediate Similarity	NPD2797	Approved
0.7315	Intermediate Similarity	NPD3539	Phase 1
0.7315	Intermediate Similarity	NPD6099	Approved
0.7315	Intermediate Similarity	NPD6100	Approved
0.7313	Intermediate Similarity	NPD5535	Approved
0.7312	Intermediate Similarity	NPD7075	Discontinued
0.731	Intermediate Similarity	NPD1296	Phase 2
0.731	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.7305	Intermediate Similarity	NPD4359	Approved
0.7305	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7297	Intermediate Similarity	NPD6111	Discontinued
0.7296	Intermediate Similarity	NPD5402	Approved
0.7292	Intermediate Similarity	NPD6832	Phase 2
0.729	Intermediate Similarity	NPD920	Approved
0.7289	Intermediate Similarity	NPD7074	Phase 3
0.7286	Intermediate Similarity	NPD1610	Phase 2
0.7285	Intermediate Similarity	NPD1243	Approved
0.7279	Intermediate Similarity	NPD1933	Approved
0.7278	Intermediate Similarity	NPD6801	Discontinued
0.7273	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.7267	Intermediate Similarity	NPD3540	Phase 1
0.7262	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.726	Intermediate Similarity	NPD4062	Phase 3
0.7246	Intermediate Similarity	NPD1894	Discontinued
0.7229	Intermediate Similarity	NPD7054	Approved
0.7219	Intermediate Similarity	NPD5958	Discontinued
0.7215	Intermediate Similarity	NPD7411	Suspended
0.7215	Intermediate Similarity	NPD6873	Phase 2
0.7214	Intermediate Similarity	NPD3847	Discontinued
0.7208	Intermediate Similarity	NPD1511	Approved
0.7202	Intermediate Similarity	NPD7685	Pre-registration
0.72	Intermediate Similarity	NPD2935	Discontinued
0.7197	Intermediate Similarity	NPD1358	Approved
0.7194	Intermediate Similarity	NPD5691	Approved
0.7192	Intermediate Similarity	NPD3764	Approved
0.7192	Intermediate Similarity	NPD3268	Approved
0.7188	Intermediate Similarity	NPD6374	Clinical (unspecified phase)
0.7186	Intermediate Similarity	NPD7472	Approved
0.7179	Intermediate Similarity	NPD5403	Approved
0.7162	Intermediate Similarity	NPD447	Suspended
0.7161	Intermediate Similarity	NPD5401	Approved
0.7161	Intermediate Similarity	NPD642	Clinical (unspecified phase)
0.7152	Intermediate Similarity	NPD6003	Clinical (unspecified phase)
0.7152	Intermediate Similarity	NPD6006	Clinical (unspecified phase)
0.7152	Intermediate Similarity	NPD4380	Phase 2
0.7152	Intermediate Similarity	NPD6005	Phase 3
0.7152	Intermediate Similarity	NPD6002	Phase 3
0.7152	Intermediate Similarity	NPD6004	Phase 3
0.7152	Intermediate Similarity	NPD7028	Phase 2
0.7143	Intermediate Similarity	NPD643	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD5019	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD7768	Phase 2
0.7134	Intermediate Similarity	NPD1653	Approved
0.7133	Intermediate Similarity	NPD1876	Approved
0.7133	Intermediate Similarity	NPD2799	Discontinued
0.7133	Intermediate Similarity	NPD1510	Phase 2
0.7133	Intermediate Similarity	NPD7033	Discontinued
0.7121	Intermediate Similarity	NPD3134	Approved
0.7115	Intermediate Similarity	NPD1512	Approved
0.7115	Intermediate Similarity	NPD7314	Clinical (unspecified phase)
0.7114	Intermediate Similarity	NPD6653	Approved
0.7111	Intermediate Similarity	NPD7680	Approved
0.7105	Intermediate Similarity	NPD4534	Discontinued
0.7101	Intermediate Similarity	NPD6559	Discontinued
0.7099	Intermediate Similarity	NPD6971	Discontinued
0.7095	Intermediate Similarity	NPD1240	Approved
0.7089	Intermediate Similarity	NPD4005	Discontinued
0.7086	Intermediate Similarity	NPD1551	Phase 2
0.7081	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.7075	Intermediate Similarity	NPD5110	Phase 2
0.7075	Intermediate Similarity	NPD5109	Approved
0.7075	Intermediate Similarity	NPD5111	Phase 2
0.7067	Intermediate Similarity	NPD7097	Phase 1
0.7063	Intermediate Similarity	NPD4749	Approved
0.7059	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD7808	Phase 3
0.7051	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7047	Intermediate Similarity	NPD1899	Clinical (unspecified phase)
0.7047	Intermediate Similarity	NPD3657	Discovery
0.7047	Intermediate Similarity	NPD4618	Approved
0.7047	Intermediate Similarity	NPD4622	Approved
0.7042	Intermediate Similarity	NPD422	Phase 1
0.7041	Intermediate Similarity	NPD6797	Phase 2
0.7039	Intermediate Similarity	NPD7266	Discontinued
0.7039	Intermediate Similarity	NPD5763	Approved
0.7039	Intermediate Similarity	NPD5762	Approved
0.7039	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7039	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7034	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7034	Intermediate Similarity	NPD5647	Approved
0.7029	Intermediate Similarity	NPD7157	Approved
0.7027	Intermediate Similarity	NPD4870	Approved
0.7025	Intermediate Similarity	NPD4210	Discontinued
0.7021	Intermediate Similarity	NPD1778	Approved
0.7019	Intermediate Similarity	NPD5563	Clinical (unspecified phase)
0.7019	Intermediate Similarity	NPD8455	Phase 2
0.7013	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.7013	Intermediate Similarity	NPD8166	Discontinued
0.7012	Intermediate Similarity	NPD6746	Phase 2
0.7007	Intermediate Similarity	NPD1241	Discontinued
0.7006	Intermediate Similarity	NPD6273	Approved
0.7	Intermediate Similarity	NPD1607	Approved
0.7	Intermediate Similarity	NPD2653	Approved
0.7	Intermediate Similarity	NPD7251	Discontinued
0.7	Intermediate Similarity	NPD1548	Phase 1

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