NPASS Compound

Structure

NPC246566 OpenBabel07101719142D 34 35 0 0 1 0 0 0 0 0999 V2000 -0.8420 2.4306 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6839 -1.9444 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6524 0.9722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5259 1.4583 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6246 0.9722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3679 0.9722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6524 2.6562 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8420 1.4583 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6839 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2219 1.8142 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6839 0.9722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1663 1.8142 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1108 1.8142 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6246 2.6562 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.9722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8420 -0.4861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2098 1.4583 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8938 1.4583 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8938 2.4306 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5777 0.4861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7358 0.9722 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 12.0830 1.8142 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 11.1108 3.4981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2098 2.4306 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8420 -0.4861 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0518 2.9167 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7358 2.9167 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4197 0.9722 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5777 -0.4861 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2496 0.1303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8420 1.4583 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8420 -1.4583 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0518 0.9722 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 32 1 0 0 0 0 2 33 1 0 0 0 0 3 5 2 0 0 0 0 3 12 1 0 0 0 0 4 6 2 0 0 0 0 4 11 1 0 0 0 0 5 13 1 0 0 0 0 6 17 1 0 0 0 0 7 12 2 0 0 0 0 7 14 1 0 0 0 0 8 11 2 0 0 0 0 8 15 1 0 0 0 0 9 11 1 0 0 0 0 9 16 2 0 0 0 0 10 12 1 0 0 0 0 10 22 1 0 0 0 0 13 14 2 0 0 0 0 13 23 1 0 0 0 0 14 24 1 0 0 0 0 15 18 2 0 0 0 0 15 32 1 0 0 0 0 16 18 1 0 0 0 0 16 33 1 0 0 0 0 17 25 2 0 0 0 0 17 34 1 0 0 0 0 18 26 1 0 0 0 0 19 20 1 6 0 0 0 19 22 1 0 0 0 0 19 34 1 0 0 0 0 20 27 2 0 0 0 0 20 28 1 0 0 0 0 21 22 1 0 0 0 0 21 29 2 0 0 0 0 21 30 1 0 0 0 0 22 31 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	478.11
Volume:	451.073
LogP:	1.422
LogD:	1.807
LogS:	-2.537
# Rotatable Bonds:	11
TPSA:	200.28
# H-Bond Aceptor:	12
# H-Bond Donor:	6
# Rings:	2
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.16
Synthetic Accessibility Score:	3.607
Fsp3:	0.227
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	2
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.26
MDCK Permeability:	2.7136133212479763e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.114
Human Intestinal Absorption (HIA):	0.841
20% Bioavailability (F20%):	0.994
30% Bioavailability (F30%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.088
Plasma Protein Binding (PPB):	96.46316528320312%
Volume Distribution (VD):	0.33
Pgp-substrate:	6.524063587188721%

ADMET: Metabolism

CYP1A2-inhibitor:	0.034
CYP1A2-substrate:	0.082
CYP2C19-inhibitor:	0.028
CYP2C19-substrate:	0.044
CYP2C9-inhibitor:	0.161
CYP2C9-substrate:	0.349
CYP2D6-inhibitor:	0.008
CYP2D6-substrate:	0.144
CYP3A4-inhibitor:	0.047
CYP3A4-substrate:	0.016

ADMET: Excretion

Clearance (CL):	2.374
Half-life (T1/2):	0.964

ADMET: Toxicity

hERG Blockers:	0.014
Human Hepatotoxicity (H-HT):	0.122
Drug-inuced Liver Injury (DILI):	0.403
AMES Toxicity:	0.014
Rat Oral Acute Toxicity:	0.011
Maximum Recommended Daily Dose:	0.022
Skin Sensitization:	0.72
Carcinogencity:	0.059
Eye Corrosion:	0.003
Eye Irritation:	0.175
Respiratory Toxicity:	0.027

Download Data

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

Natural Product: NPC246566

Natural Product ID:	NPC246566
*Common Name:**	Cimicifugic Acid I
IUPAC Name:	(2R,3S)-2-[(3,4-dihydroxyphenyl)methyl]-2-hydroxy-3-[(E)-3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-enoyl]oxybutanedioic acid
Synonyms:	Cimicifugic Acid I
Standard InCHIKey:	OGOVVRHSMHRFIK-MYEWIJLCSA-N
Standard InCHI:	InChI=1S/C22H22O12/c1-32-15-8-11(9-16(33-2)18(15)26)4-6-17(25)34-19(20(27)28)22(31,21(29)30)10-12-3-5-13(23)14(24)7-12/h3-9,19,23-24,26,31H,10H2,1-2H3,(H,27,28)(H,29,30)/b6-4+/t19-,22-/m1/s1
SMILES:	COc1cc(/C=C/C(=O)O[C@H](C(=O)O)[C@](Cc2ccc(c(c2)O)O)(C(=O)O)O)cc(c1O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1094269
PubChem CID:	46209910
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric 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
NPO30530	Cimicifuga dahurica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20192237]
NPO32999	cimicifuga heracleifolia	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20192237]
NPO30530	Cimicifuga dahurica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30530	Cimicifuga dahurica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified		IC50	=	143000.0	nM	PMID[465974]

☑ 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 NPC246566 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	347
0.1-0.2	1411
0.2-0.3	3715
0.3-0.4	8222
0.4-0.5	9654
0.5-0.6	4157
0.6-0.7	5602
0.7-0.8	7744
0.8-0.85	1692
0.85-0.9	135
0.9-0.95	10
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC95498
0.9653	High Similarity	NPC221383
0.9653	High Similarity	NPC143892
0.9653	High Similarity	NPC299090
0.9653	High Similarity	NPC283081
0.9514	High Similarity	NPC258671
0.9514	High Similarity	NPC53884
0.9444	High Similarity	NPC304956
0.9205	High Similarity	NPC477299
0.92	High Similarity	NPC163883
0.92	High Similarity	NPC93498
0.9167	High Similarity	NPC156709
0.9167	High Similarity	NPC179505
0.9167	High Similarity	NPC288452
0.9167	High Similarity	NPC289690
0.9139	High Similarity	NPC19380
0.9139	High Similarity	NPC146277
0.9073	High Similarity	NPC476434
0.9054	High Similarity	NPC98356
0.9032	High Similarity	NPC44507
0.9028	High Similarity	NPC279676
0.9028	High Similarity	NPC67349
0.9026	High Similarity	NPC223335
0.9026	High Similarity	NPC40920
0.902	High Similarity	NPC145425
0.9007	High Similarity	NPC300329
0.9	High Similarity	NPC125570
0.8993	High Similarity	NPC229264
0.8968	High Similarity	NPC469654
0.8947	High Similarity	NPC75695
0.894	High Similarity	NPC221091
0.894	High Similarity	NPC259576
0.894	High Similarity	NPC32197
0.8933	High Similarity	NPC192568
0.8933	High Similarity	NPC1580
0.8933	High Similarity	NPC471076
0.8896	High Similarity	NPC476642
0.8889	High Similarity	NPC473236
0.8854	High Similarity	NPC112418
0.8851	High Similarity	NPC477697
0.8851	High Similarity	NPC477696
0.8851	High Similarity	NPC106920
0.8851	High Similarity	NPC470811
0.8851	High Similarity	NPC273657
0.8844	High Similarity	NPC470991
0.8839	High Similarity	NPC470896
0.8839	High Similarity	NPC473275
0.8819	High Similarity	NPC106406
0.8816	High Similarity	NPC473091
0.8797	High Similarity	NPC471745
0.8792	High Similarity	NPC160378
0.879	High Similarity	NPC471744
0.879	High Similarity	NPC130955
0.8784	High Similarity	NPC253722
0.8784	High Similarity	NPC31751
0.8784	High Similarity	NPC253481
0.8766	High Similarity	NPC44730
0.8766	High Similarity	NPC199773
0.8766	High Similarity	NPC327225
0.8758	High Similarity	NPC32079
0.875	High Similarity	NPC168799
0.875	High Similarity	NPC155209
0.8742	High Similarity	NPC322660
0.8733	High Similarity	NPC223185
0.871	High Similarity	NPC25127
0.871	High Similarity	NPC287504
0.871	High Similarity	NPC136757
0.8701	High Similarity	NPC477699
0.8693	High Similarity	NPC306343
0.869	High Similarity	NPC135127
0.8688	High Similarity	NPC88243
0.8684	High Similarity	NPC98009
0.8684	High Similarity	NPC472969
0.8681	High Similarity	NPC25581
0.8681	High Similarity	NPC5419
0.8681	High Similarity	NPC18074
0.8681	High Similarity	NPC61
0.8675	High Similarity	NPC213482
0.8671	High Similarity	NPC53889
0.8671	High Similarity	NPC301089
0.8667	High Similarity	NPC27159
0.8667	High Similarity	NPC183824
0.8662	High Similarity	NPC471515
0.8662	High Similarity	NPC472860
0.8662	High Similarity	NPC67876
0.8662	High Similarity	NPC471479
0.8654	High Similarity	NPC286052
0.865	High Similarity	NPC476370
0.8649	High Similarity	NPC26241
0.8649	High Similarity	NPC476820
0.8649	High Similarity	NPC322021
0.8649	High Similarity	NPC303683
0.8649	High Similarity	NPC205751
0.8649	High Similarity	NPC474875
0.8649	High Similarity	NPC295492
0.8649	High Similarity	NPC147379
0.8649	High Similarity	NPC274891
0.8649	High Similarity	NPC476819
0.8636	High Similarity	NPC477700
0.8634	High Similarity	NPC471823
0.8627	High Similarity	NPC474903
0.8627	High Similarity	NPC42464
0.8625	High Similarity	NPC173729
0.8625	High Similarity	NPC272750
0.8625	High Similarity	NPC134047
0.8625	High Similarity	NPC223006
0.8618	High Similarity	NPC472333
0.8618	High Similarity	NPC208507
0.8616	High Similarity	NPC349525
0.8611	High Similarity	NPC108553
0.8611	High Similarity	NPC198388
0.8609	High Similarity	NPC474982
0.8608	High Similarity	NPC87317
0.8608	High Similarity	NPC55738
0.86	High Similarity	NPC220664
0.86	High Similarity	NPC277315
0.86	High Similarity	NPC43158
0.86	High Similarity	NPC303090
0.86	High Similarity	NPC472016
0.86	High Similarity	NPC192831
0.86	High Similarity	NPC37331
0.86	High Similarity	NPC284948
0.86	High Similarity	NPC258469
0.86	High Similarity	NPC319628
0.86	High Similarity	NPC285550
0.8599	High Similarity	NPC227062
0.8599	High Similarity	NPC474638
0.8599	High Similarity	NPC265511
0.8599	High Similarity	NPC471500
0.8598	High Similarity	NPC476374
0.8591	High Similarity	NPC100675
0.859	High Similarity	NPC298802
0.8581	High Similarity	NPC152942
0.8581	High Similarity	NPC284409
0.8581	High Similarity	NPC37250
0.8581	High Similarity	NPC219428
0.8581	High Similarity	NPC302857
0.8581	High Similarity	NPC151425
0.8581	High Similarity	NPC56184
0.8581	High Similarity	NPC278068
0.8581	High Similarity	NPC142703
0.858	High Similarity	NPC283041
0.8571	High Similarity	NPC470916
0.8571	High Similarity	NPC90431
0.8571	High Similarity	NPC191930
0.8571	High Similarity	NPC471788
0.8562	High Similarity	NPC139839
0.8562	High Similarity	NPC144557
0.8562	High Similarity	NPC102934
0.8562	High Similarity	NPC43123
0.8562	High Similarity	NPC252402
0.8562	High Similarity	NPC294972
0.8562	High Similarity	NPC42797
0.8553	High Similarity	NPC239966
0.8553	High Similarity	NPC474799
0.8553	High Similarity	NPC24627
0.8553	High Similarity	NPC292415
0.8553	High Similarity	NPC203020
0.8544	High Similarity	NPC114179
0.8544	High Similarity	NPC156818
0.8544	High Similarity	NPC160512
0.8544	High Similarity	NPC35598
0.8544	High Similarity	NPC289322
0.8544	High Similarity	NPC38779
0.8544	High Similarity	NPC52530
0.8544	High Similarity	NPC68324
0.8544	High Similarity	NPC222689
0.8543	High Similarity	NPC114242
0.8543	High Similarity	NPC50221
0.8543	High Similarity	NPC16353
0.8542	High Similarity	NPC32626
0.8542	High Similarity	NPC237506
0.8542	High Similarity	NPC217052
0.8542	High Similarity	NPC329344
0.8535	High Similarity	NPC38699
0.8535	High Similarity	NPC82592
0.8535	High Similarity	NPC16082
0.8533	High Similarity	NPC471027
0.8533	High Similarity	NPC13818
0.8533	High Similarity	NPC206095
0.8533	High Similarity	NPC224389
0.8533	High Similarity	NPC35702
0.8533	High Similarity	NPC477335
0.8533	High Similarity	NPC297517
0.8528	High Similarity	NPC280493
0.8526	High Similarity	NPC474656
0.8526	High Similarity	NPC178574
0.8526	High Similarity	NPC289968
0.8526	High Similarity	NPC65591
0.8523	High Similarity	NPC267291
0.8523	High Similarity	NPC474784
0.8519	High Similarity	NPC477517
0.8519	High Similarity	NPC20237
0.8516	High Similarity	NPC62354
0.8516	High Similarity	NPC243891
0.8509	High Similarity	NPC249181
0.8509	High Similarity	NPC472582
0.8509	High Similarity	NPC291977
0.8506	High Similarity	NPC478242
0.8506	High Similarity	NPC145569

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 NPC246566 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	305
0.1-0.2	867
0.2-0.3	1792
0.3-0.4	2590
0.4-0.5	1872
0.5-0.6	1038
0.6-0.7	528
0.7-0.8	136
0.8-0.85	21
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.86	High Similarity	NPD6190	Approved
0.8599	High Similarity	NPD3882	Suspended
0.8535	High Similarity	NPD3817	Phase 2
0.8481	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.8408	Intermediate Similarity	NPD1934	Approved
0.8345	Intermediate Similarity	NPD3027	Phase 3
0.8344	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.8344	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.8344	Intermediate Similarity	NPD6166	Phase 2
0.8323	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.8313	Intermediate Similarity	NPD7075	Discontinued
0.8261	Intermediate Similarity	NPD6234	Discontinued
0.8242	Intermediate Similarity	NPD3818	Discontinued
0.8239	Intermediate Similarity	NPD2801	Approved
0.8239	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.8221	Intermediate Similarity	NPD6232	Discontinued
0.8187	Intermediate Similarity	NPD5402	Approved
0.8129	Intermediate Similarity	NPD6799	Approved
0.8125	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.8121	Intermediate Similarity	NPD230	Phase 1
0.8095	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.8095	Intermediate Similarity	NPD6797	Phase 2
0.8072	Intermediate Similarity	NPD7473	Discontinued
0.8063	Intermediate Similarity	NPD6801	Discontinued
0.8063	Intermediate Similarity	NPD37	Approved
0.8047	Intermediate Similarity	NPD7251	Discontinued
0.8036	Intermediate Similarity	NPD7074	Phase 3
0.8025	Intermediate Similarity	NPD4965	Approved
0.8025	Intermediate Similarity	NPD4967	Phase 2
0.8025	Intermediate Similarity	NPD1512	Approved
0.8025	Intermediate Similarity	NPD4966	Approved
0.8	Intermediate Similarity	NPD7808	Phase 3
0.7976	Intermediate Similarity	NPD7054	Approved
0.7975	Intermediate Similarity	NPD5403	Approved
0.7965	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7937	Intermediate Similarity	NPD6599	Discontinued
0.7937	Intermediate Similarity	NPD4380	Phase 2
0.7929	Intermediate Similarity	NPD7472	Approved
0.7917	Intermediate Similarity	NPD7228	Approved
0.7901	Intermediate Similarity	NPD1465	Phase 2
0.7898	Intermediate Similarity	NPD1511	Approved
0.7862	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.7848	Intermediate Similarity	NPD5401	Approved
0.7844	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7815	Intermediate Similarity	NPD1613	Approved
0.7815	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7812	Intermediate Similarity	NPD1653	Approved
0.7808	Intermediate Similarity	NPD4379	Clinical (unspecified phase)
0.7792	Intermediate Similarity	NPD2935	Discontinued
0.7785	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7765	Intermediate Similarity	NPD5844	Phase 1
0.7758	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.7748	Intermediate Similarity	NPD6233	Phase 2
0.7742	Intermediate Similarity	NPD7266	Discontinued
0.7736	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7711	Intermediate Similarity	NPD919	Approved
0.7707	Intermediate Similarity	NPD4628	Phase 3
0.7706	Intermediate Similarity	NPD3751	Discontinued
0.7683	Intermediate Similarity	NPD7819	Suspended
0.7682	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.7682	Intermediate Similarity	NPD6798	Discontinued
0.7667	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7665	Intermediate Similarity	NPD5494	Approved
0.7661	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7647	Intermediate Similarity	NPD447	Suspended
0.7647	Intermediate Similarity	NPD6355	Discontinued
0.764	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.7633	Intermediate Similarity	NPD3926	Phase 2
0.763	Intermediate Similarity	NPD6559	Discontinued
0.763	Intermediate Similarity	NPD7685	Pre-registration
0.7619	Intermediate Similarity	NPD7199	Phase 2
0.7613	Intermediate Similarity	NPD1510	Phase 2
0.76	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7595	Intermediate Similarity	NPD1878	Clinical (unspecified phase)
0.7582	Intermediate Similarity	NPD1240	Approved
0.7582	Intermediate Similarity	NPD943	Approved
0.758	Intermediate Similarity	NPD1549	Phase 2
0.758	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7564	Intermediate Similarity	NPD1551	Phase 2
0.7561	Intermediate Similarity	NPD7411	Suspended
0.7529	Intermediate Similarity	NPD5242	Approved
0.7528	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7516	Intermediate Similarity	NPD4062	Phase 3
0.7516	Intermediate Similarity	NPD2532	Approved
0.7516	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7516	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7516	Intermediate Similarity	NPD2534	Approved
0.7516	Intermediate Similarity	NPD2533	Approved
0.7515	Intermediate Similarity	NPD1247	Approved
0.75	Intermediate Similarity	NPD7095	Approved
0.7485	Intermediate Similarity	NPD7768	Phase 2
0.7484	Intermediate Similarity	NPD1607	Approved
0.7484	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7484	Intermediate Similarity	NPD3750	Approved
0.7483	Intermediate Similarity	NPD9494	Approved
0.7471	Intermediate Similarity	NPD3787	Discontinued
0.7468	Intermediate Similarity	NPD4060	Phase 1
0.7453	Intermediate Similarity	NPD4357	Discontinued
0.7452	Intermediate Similarity	NPD2796	Approved
0.7429	Intermediate Similarity	NPD7240	Approved
0.7425	Intermediate Similarity	NPD5353	Approved
0.7416	Intermediate Similarity	NPD8434	Phase 2
0.7407	Intermediate Similarity	NPD7410	Clinical (unspecified phase)
0.7383	Intermediate Similarity	NPD9269	Phase 2
0.7375	Intermediate Similarity	NPD4110	Phase 3
0.7375	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7349	Intermediate Similarity	NPD6385	Approved
0.7349	Intermediate Similarity	NPD6386	Approved
0.7333	Intermediate Similarity	NPD2983	Phase 2
0.7333	Intermediate Similarity	NPD2982	Phase 2
0.7329	Intermediate Similarity	NPD5536	Phase 2
0.7321	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.731	Intermediate Similarity	NPD8127	Discontinued
0.7303	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7283	Intermediate Similarity	NPD7852	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD651	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD7033	Discontinued
0.7273	Intermediate Similarity	NPD5953	Discontinued
0.7267	Intermediate Similarity	NPD8166	Discontinued
0.7267	Intermediate Similarity	NPD2981	Phase 2
0.7255	Intermediate Similarity	NPD3018	Phase 2
0.725	Intermediate Similarity	NPD4534	Discontinued
0.7246	Intermediate Similarity	NPD7615	Clinical (unspecified phase)
0.7235	Intermediate Similarity	NPD3749	Approved
0.7234	Intermediate Similarity	NPD7435	Discontinued
0.7229	Intermediate Similarity	NPD3226	Approved
0.7229	Intermediate Similarity	NPD3455	Phase 2
0.7226	Intermediate Similarity	NPD3764	Approved
0.7209	Intermediate Similarity	NPD6959	Discontinued
0.7208	Intermediate Similarity	NPD6832	Phase 2
0.7205	Intermediate Similarity	NPD7421	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD422	Phase 1
0.7197	Intermediate Similarity	NPD1933	Approved
0.7197	Intermediate Similarity	NPD4340	Discontinued
0.717	Intermediate Similarity	NPD2799	Discontinued
0.717	Intermediate Similarity	NPD3748	Approved
0.7153	Intermediate Similarity	NPD228	Approved
0.7152	Intermediate Similarity	NPD1608	Approved
0.7143	Intermediate Similarity	NPD5958	Discontinued
0.7127	Intermediate Similarity	NPD8150	Discontinued
0.7125	Intermediate Similarity	NPD2438	Suspended
0.7124	Intermediate Similarity	NPD1203	Approved
0.7124	Intermediate Similarity	NPD2797	Approved
0.7117	Intermediate Similarity	NPD2354	Approved
0.7117	Intermediate Similarity	NPD3887	Approved
0.7114	Intermediate Similarity	NPD9268	Approved
0.7112	Intermediate Similarity	NPD7237	Clinical (unspecified phase)
0.7108	Intermediate Similarity	NPD920	Approved
0.7107	Intermediate Similarity	NPD7097	Phase 1
0.7099	Intermediate Similarity	NPD1652	Phase 2
0.7097	Intermediate Similarity	NPD8090	Clinical (unspecified phase)
0.7097	Intermediate Similarity	NPD4908	Phase 1
0.7095	Intermediate Similarity	NPD7549	Discontinued
0.7091	Intermediate Similarity	NPD3146	Approved
0.7091	Intermediate Similarity	NPD3688	Clinical (unspecified phase)
0.7089	Intermediate Similarity	NPD5123	Clinical (unspecified phase)
0.7089	Intermediate Similarity	NPD1899	Clinical (unspecified phase)
0.7089	Intermediate Similarity	NPD5124	Phase 1
0.7074	Intermediate Similarity	NPD6782	Approved
0.7074	Intermediate Similarity	NPD6776	Approved
0.7074	Intermediate Similarity	NPD6779	Approved
0.7074	Intermediate Similarity	NPD6778	Approved
0.7074	Intermediate Similarity	NPD6781	Approved
0.7074	Intermediate Similarity	NPD6780	Approved
0.7074	Intermediate Similarity	NPD6777	Approved
0.7062	Intermediate Similarity	NPD7286	Phase 2
0.7056	Intermediate Similarity	NPD8313	Approved
0.7056	Intermediate Similarity	NPD8312	Approved
0.7055	Intermediate Similarity	NPD5283	Phase 1
0.7053	Intermediate Similarity	NPD7680	Approved
0.7047	Intermediate Similarity	NPD9545	Approved
0.7039	Intermediate Similarity	NPD7038	Approved
0.7039	Intermediate Similarity	NPD7039	Approved
0.7035	Intermediate Similarity	NPD6971	Discontinued
0.7025	Intermediate Similarity	NPD7966	Clinical (unspecified phase)
0.7019	Intermediate Similarity	NPD6099	Approved
0.7019	Intermediate Similarity	NPD6100	Approved
0.7019	Intermediate Similarity	NPD6032	Approved
0.701	Intermediate Similarity	NPD7874	Approved
0.701	Intermediate Similarity	NPD7875	Clinical (unspecified phase)
0.7006	Intermediate Similarity	NPD3268	Approved
0.7006	Intermediate Similarity	NPD2313	Discontinued
0.7006	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.6989	Remote Similarity	NPD7784	Clinical (unspecified phase)
0.6988	Remote Similarity	NPD642	Clinical (unspecified phase)
0.6988	Remote Similarity	NPD7004	Clinical (unspecified phase)
0.6975	Remote Similarity	NPD5762	Approved
0.6975	Remote Similarity	NPD2346	Discontinued
0.6975	Remote Similarity	NPD5763	Approved
0.6974	Remote Similarity	NPD1610	Phase 2
0.6974	Remote Similarity	NPD1535	Discovery
0.6973	Remote Similarity	NPD7296	Approved
0.6971	Remote Similarity	NPD5711	Approved
0.6971	Remote Similarity	NPD5710	Approved
0.6971	Remote Similarity	NPD7229	Phase 3
0.6968	Remote Similarity	NPD5647	Approved
0.6959	Remote Similarity	NPD8455	Phase 2
0.6959	Remote Similarity	NPD8151	Discontinued
0.6957	Remote Similarity	NPD4308	Phase 3
0.6954	Remote Similarity	NPD17	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