NPASS Compound

Structure

CID256422 OpenBabel06191716062D 41 45 0 0 1 0 0 0 0 0999 V2000 6.3472 -5.7171 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1854 -6.8264 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4910 -3.8917 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8581 -4.8699 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2866 -0.9569 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3689 -5.7171 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7450 0.5105 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0326 -3.4025 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1854 -3.8917 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8978 0.0214 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5922 0.0214 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8798 -3.8917 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3382 -5.3591 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7450 -2.4243 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6438 -2.4243 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8798 -6.8264 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9729 0.1023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0326 -6.3373 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4910 -4.8699 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1854 -4.8699 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8978 -0.9569 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7450 -1.4460 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2034 -2.9134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8978 -2.9134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5922 -0.9569 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6438 -1.4460 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0506 -2.4243 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0506 -1.4460 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0326 -5.3591 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2034 -0.9569 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2034 -4.8699 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8798 -4.8699 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8978 -3.8917 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.8798 -7.8047 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0506 -5.3591 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7450 -4.3808 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0506 -4.3808 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4394 -1.4460 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3708 -0.7914 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 0.6438 -5.3591 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 2 0 0 0 0 2 18 2 0 0 0 0 5 38 1 0 0 0 0 6 32 1 0 0 0 0 7 10 2 0 0 0 0 7 11 1 0 0 0 0 8 9 1 0 0 0 0 8 12 1 0 0 0 0 9 20 2 0 0 0 0 10 21 1 0 0 0 0 11 25 2 0 0 0 0 12 32 1 0 0 0 0 13 19 1 0 0 0 0 13 20 1 0 0 0 0 14 22 2 0 0 0 0 14 24 1 0 0 0 0 15 23 2 0 0 0 0 15 26 1 0 0 0 0 16 18 1 0 0 0 0 16 34 2 0 0 0 0 17 39 1 0 0 0 0 17 40 1 0 0 0 0 18 29 1 0 0 0 0 19 3 1 1 0 0 0 19 41 1 0 0 0 0 20 29 1 0 0 0 0 21 22 1 0 0 0 0 21 28 2 0 0 0 0 22 25 1 0 0 0 0 23 27 1 0 0 0 0 23 31 1 0 0 0 0 24 27 2 0 0 0 0 24 33 1 0 0 0 0 25 38 1 0 0 0 0 26 30 2 0 0 0 0 26 39 1 0 0 0 0 27 28 1 0 0 0 0 28 30 1 0 0 0 0 29 32 1 6 0 0 0 30 40 1 0 0 0 0 31 35 2 0 0 0 0 31 41 1 0 0 0 0 32 4 1 1 0 0 0 33 36 2 0 0 0 0 33 37 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	557.2
Volume:	566.29
LogP:	6.731
LogD:	4.113
LogS:	-8.013
# Rotatable Bonds:	10
TPSA:	114.2
# H-Bond Aceptor:	9
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.053
Synthetic Accessibility Score:	4.597
Fsp3:	0.312
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	3
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.744
MDCK Permeability:	2.2725502276443876e-05
Pgp-inhibitor:	0.95
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.01

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016
Plasma Protein Binding (PPB):	93.64226531982422%
Volume Distribution (VD):	0.84
Pgp-substrate:	3.7613635063171387%

ADMET: Metabolism

CYP1A2-inhibitor:	0.713
CYP1A2-substrate:	0.136
CYP2C19-inhibitor:	0.971
CYP2C19-substrate:	0.106
CYP2C9-inhibitor:	0.957
CYP2C9-substrate:	0.927
CYP2D6-inhibitor:	0.912
CYP2D6-substrate:	0.306
CYP3A4-inhibitor:	0.938
CYP3A4-substrate:	0.106

ADMET: Excretion

Clearance (CL):	5.833
Half-life (T1/2):	0.025

ADMET: Toxicity

hERG Blockers:	0.002
Human Hepatotoxicity (H-HT):	0.024
Drug-inuced Liver Injury (DILI):	0.881
AMES Toxicity:	0.966
Rat Oral Acute Toxicity:	0.065
Maximum Recommended Daily Dose:	0.961
Skin Sensitization:	0.946
Carcinogencity:	0.953
Eye Corrosion:	0.03
Eye Irritation:	0.426
Respiratory Toxicity:	0.983

Download Data

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

Natural Product: NPC256422

Natural Product ID:	NPC256422
*Common Name:**	Aristophyllide A
IUPAC Name:	[(2S)-1-[(5R,6R)-5-ethenyl-5-methyl-6-(3-oxoprop-1-en-2-yl)cyclohexen-1-yl]propan-2-yl] 8-methoxy-6-nitronaphtho[2,1-g][1,3]benzodioxole-5-carboxylate
Synonyms:
Standard InCHIKey:	XXQZGCCUBVSBKJ-ZUECTMELSA-N
Standard InCHI:	InChI=1S/C32H31NO8/c1-6-32(4)12-8-9-20(29(32)18(2)16-34)13-19(3)41-31(35)23-15-26-30(40-17-39-26)28-21-10-7-11-25(38-5)22(21)14-24(27(23)28)33(36)37/h6-7,9-11,14-16,19,29H,1-2,8,12-13,17H2,3-5H3/t19-,29+,32-/m0/s1
SMILES:	C=C[C@@]1(C)CCC=C(C[C@H](C)OC(=O)c2cc3c(c4c5cccc(c5cc(c24)N(=O)=O)OC)OCO3)[C@H]1C(=C)C=O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL449419
PubChem CID:	10840539
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000025] Phenanthrenes and derivatives [CHEMONTID:0002664] Aristolochic 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
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10075784]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	root	n.a.	PMID[10096848]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	root and stem	n.a.	n.a.	PMID[10096848]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	stem	n.a.	PMID[10096848]
NPO7557	Aristolochia mollissima	Species	Aristolochiaceae	Eukaryota	n.a.	amniotic fluid	n.a.	Database[Article]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7557	Aristolochia mollissima	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7557	Aristolochia mollissima	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16163	Aristolochia heterophylla	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7557	Aristolochia mollissima	Species	Aristolochiaceae	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
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	5100.0	nM	PMID[558149]

☑ 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 NPC256422 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	461
0.1-0.2	2072
0.2-0.3	4843
0.3-0.4	11530
0.4-0.5	7022
0.5-0.6	12602
0.6-0.7	4077
0.7-0.8	74
0.8-0.85	0
0.85-0.9	5
0.9-0.95	3
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID
0.9742	High Similarity	NPC124658
0.9742	High Similarity	NPC227361
0.9639	High Similarity	NPC186569
0.9639	High Similarity	NPC61731
0.933	High Similarity	NPC38961
0.9141	High Similarity	NPC85661
0.9091	High Similarity	NPC46679
0.9045	High Similarity	NPC171882
0.9045	High Similarity	NPC121510
0.9005	High Similarity	NPC91234
0.8916	High Similarity	NPC290227
0.8873	High Similarity	NPC240684
0.7778	Intermediate Similarity	NPC55470
0.7746	Intermediate Similarity	NPC90185
0.7477	Intermediate Similarity	NPC207971
0.7454	Intermediate Similarity	NPC222561
0.7454	Intermediate Similarity	NPC308943
0.7423	Intermediate Similarity	NPC118332
0.7419	Intermediate Similarity	NPC100573
0.7419	Intermediate Similarity	NPC207873
0.7406	Intermediate Similarity	NPC193906
0.7406	Intermediate Similarity	NPC23080
0.7404	Intermediate Similarity	NPC296742
0.7404	Intermediate Similarity	NPC312531
0.7395	Intermediate Similarity	NPC159101
0.7361	Intermediate Similarity	NPC268077
0.7356	Intermediate Similarity	NPC224293
0.7327	Intermediate Similarity	NPC471923
0.7321	Intermediate Similarity	NPC112676
0.7308	Intermediate Similarity	NPC69213
0.7291	Intermediate Similarity	NPC473531
0.7291	Intermediate Similarity	NPC475453
0.729	Intermediate Similarity	NPC5374
0.7286	Intermediate Similarity	NPC125713
0.7284	Intermediate Similarity	NPC160113
0.7284	Intermediate Similarity	NPC476220
0.7273	Intermediate Similarity	NPC239113
0.7273	Intermediate Similarity	NPC115123
0.7273	Intermediate Similarity	NPC109765
0.7243	Intermediate Similarity	NPC71124
0.7236	Intermediate Similarity	NPC202495
0.722	Intermediate Similarity	NPC298449
0.7212	Intermediate Similarity	NPC249405
0.7192	Intermediate Similarity	NPC477884
0.7184	Intermediate Similarity	NPC473697
0.7183	Intermediate Similarity	NPC29472
0.7172	Intermediate Similarity	NPC54179
0.7164	Intermediate Similarity	NPC78944
0.7161	Intermediate Similarity	NPC476258
0.7161	Intermediate Similarity	NPC304837
0.7155	Intermediate Similarity	NPC227033
0.715	Intermediate Similarity	NPC260118
0.715	Intermediate Similarity	NPC19600
0.7143	Intermediate Similarity	NPC300983
0.7143	Intermediate Similarity	NPC311781
0.7143	Intermediate Similarity	NPC100420
0.7136	Intermediate Similarity	NPC52598
0.7136	Intermediate Similarity	NPC254957
0.7129	Intermediate Similarity	NPC319749
0.7115	Intermediate Similarity	NPC215747
0.7115	Intermediate Similarity	NPC192939
0.7114	Intermediate Similarity	NPC68619
0.7114	Intermediate Similarity	NPC474043
0.7109	Intermediate Similarity	NPC474009
0.7106	Intermediate Similarity	NPC154922
0.7101	Intermediate Similarity	NPC114550
0.7101	Intermediate Similarity	NPC312006
0.7101	Intermediate Similarity	NPC292712
0.7101	Intermediate Similarity	NPC265383
0.7101	Intermediate Similarity	NPC471920
0.7101	Intermediate Similarity	NPC471921
0.7101	Intermediate Similarity	NPC129930
0.7101	Intermediate Similarity	NPC471922
0.7101	Intermediate Similarity	NPC20114
0.7101	Intermediate Similarity	NPC474075
0.7094	Intermediate Similarity	NPC116838
0.7094	Intermediate Similarity	NPC22130
0.7092	Intermediate Similarity	NPC127827
0.7081	Intermediate Similarity	NPC179704
0.7072	Intermediate Similarity	NPC46990
0.7067	Intermediate Similarity	NPC316539
0.7067	Intermediate Similarity	NPC190461
0.7056	Intermediate Similarity	NPC302001
0.7056	Intermediate Similarity	NPC475722
0.7048	Intermediate Similarity	NPC28425
0.7044	Intermediate Similarity	NPC191352
0.7044	Intermediate Similarity	NPC258322
0.7044	Intermediate Similarity	NPC15212
0.7033	Intermediate Similarity	NPC193377
0.703	Intermediate Similarity	NPC325122
0.7029	Intermediate Similarity	NPC113455
0.7024	Intermediate Similarity	NPC41689
0.7019	Intermediate Similarity	NPC35680
0.7019	Intermediate Similarity	NPC287588
0.7015	Intermediate Similarity	NPC261484
0.7014	Intermediate Similarity	NPC161609
0.7014	Intermediate Similarity	NPC275690
0.7012	Intermediate Similarity	NPC120239
0.701	Intermediate Similarity	NPC280778
0.7	Intermediate Similarity	NPC119579
0.7	Intermediate Similarity	NPC196771
0.6995	Remote Similarity	NPC141440
0.6995	Remote Similarity	NPC474904
0.6991	Remote Similarity	NPC174783
0.6991	Remote Similarity	NPC470023
0.6991	Remote Similarity	NPC33256
0.699	Remote Similarity	NPC474042
0.699	Remote Similarity	NPC174734
0.6986	Remote Similarity	NPC184624
0.6986	Remote Similarity	NPC477881
0.6981	Remote Similarity	NPC219170
0.6981	Remote Similarity	NPC180253
0.698	Remote Similarity	NPC76458
0.698	Remote Similarity	NPC82733
0.697	Remote Similarity	NPC474305
0.6968	Remote Similarity	NPC244606
0.6968	Remote Similarity	NPC156728
0.6967	Remote Similarity	NPC35266
0.6967	Remote Similarity	NPC276060
0.6967	Remote Similarity	NPC477882
0.6967	Remote Similarity	NPC477880
0.6965	Remote Similarity	NPC234730
0.6964	Remote Similarity	NPC25961
0.6961	Remote Similarity	NPC469889
0.6959	Remote Similarity	NPC470021
0.6957	Remote Similarity	NPC227683
0.6952	Remote Similarity	NPC311936
0.6946	Remote Similarity	NPC472299
0.6942	Remote Similarity	NPC474301
0.6933	Remote Similarity	NPC189903
0.6933	Remote Similarity	NPC182907
0.6927	Remote Similarity	NPC215098
0.6927	Remote Similarity	NPC19948
0.6927	Remote Similarity	NPC198796
0.6927	Remote Similarity	NPC46744
0.6927	Remote Similarity	NPC73020
0.6927	Remote Similarity	NPC124302
0.6927	Remote Similarity	NPC70290
0.6927	Remote Similarity	NPC14622
0.6923	Remote Similarity	NPC285941
0.6923	Remote Similarity	NPC117911
0.6919	Remote Similarity	NPC475054
0.6919	Remote Similarity	NPC474306
0.6919	Remote Similarity	NPC24193
0.6919	Remote Similarity	NPC475848
0.6916	Remote Similarity	NPC237579
0.6916	Remote Similarity	NPC114120
0.6916	Remote Similarity	NPC167045
0.6915	Remote Similarity	NPC273578
0.6912	Remote Similarity	NPC139876
0.691	Remote Similarity	NPC476436
0.6909	Remote Similarity	NPC471489
0.6908	Remote Similarity	NPC320471
0.6908	Remote Similarity	NPC118162
0.6908	Remote Similarity	NPC83049
0.6908	Remote Similarity	NPC291742
0.6904	Remote Similarity	NPC24257
0.6904	Remote Similarity	NPC153620
0.6903	Remote Similarity	NPC477826
0.6903	Remote Similarity	NPC477827
0.6901	Remote Similarity	NPC214629
0.6897	Remote Similarity	NPC167098
0.6897	Remote Similarity	NPC477885
0.6897	Remote Similarity	NPC296044
0.6897	Remote Similarity	NPC143328
0.6895	Remote Similarity	NPC212163
0.6893	Remote Similarity	NPC308156
0.6893	Remote Similarity	NPC45943
0.6893	Remote Similarity	NPC247389
0.6891	Remote Similarity	NPC108342
0.689	Remote Similarity	NPC477883
0.6887	Remote Similarity	NPC47191
0.6878	Remote Similarity	NPC309335
0.6878	Remote Similarity	NPC239890
0.6878	Remote Similarity	NPC296540
0.6878	Remote Similarity	NPC209411
0.6878	Remote Similarity	NPC67346
0.6875	Remote Similarity	NPC311912
0.6875	Remote Similarity	NPC79322
0.6872	Remote Similarity	NPC27887
0.6872	Remote Similarity	NPC86455
0.6872	Remote Similarity	NPC137920
0.6872	Remote Similarity	NPC125134
0.6869	Remote Similarity	NPC22928
0.6869	Remote Similarity	NPC181464
0.6866	Remote Similarity	NPC308555
0.6866	Remote Similarity	NPC10429
0.6864	Remote Similarity	NPC314100
0.6864	Remote Similarity	NPC226652
0.6864	Remote Similarity	NPC72788
0.6864	Remote Similarity	NPC120671
0.6863	Remote Similarity	NPC15764
0.6861	Remote Similarity	NPC476500
0.6857	Remote Similarity	NPC85613
0.6852	Remote Similarity	NPC313063
0.6852	Remote Similarity	NPC286301
0.6849	Remote Similarity	NPC476358
0.6849	Remote Similarity	NPC17677
0.6847	Remote Similarity	NPC301897
0.6847	Remote Similarity	NPC477380

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 NPC256422 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	336
0.1-0.2	897
0.2-0.3	1142
0.3-0.4	2643
0.4-0.5	2558
0.5-0.6	1301
0.6-0.7	267
0.7-0.8	6
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
0.7391	Intermediate Similarity	NPD6723	Discontinued
0.7256	Intermediate Similarity	NPD4107	Approved
0.7215	Intermediate Similarity	NPD6296	Discontinued
0.7155	Intermediate Similarity	NPD8067	Phase 3
0.7143	Intermediate Similarity	NPD4482	Phase 3
0.7116	Intermediate Similarity	NPD7238	Clinical (unspecified phase)
0.7043	Intermediate Similarity	NPD5619	Clinical (unspecified phase)
0.6995	Remote Similarity	NPD710	Clinical (unspecified phase)
0.6955	Remote Similarity	NPD5848	Clinical (unspecified phase)
0.6951	Remote Similarity	NPD4859	Phase 1
0.6949	Remote Similarity	NPD6625	Approved
0.6946	Remote Similarity	NPD3252	Approved
0.6927	Remote Similarity	NPD4420	Approved
0.6923	Remote Similarity	NPD7597	Clinical (unspecified phase)
0.6916	Remote Similarity	NPD8397	Clinical (unspecified phase)
0.6901	Remote Similarity	NPD6793	Clinical (unspecified phase)
0.6878	Remote Similarity	NPD3057	Approved
0.6802	Remote Similarity	NPD5006	Approved
0.6802	Remote Similarity	NPD3533	Approved
0.6802	Remote Similarity	NPD5005	Approved
0.6802	Remote Similarity	NPD2972	Approved
0.6796	Remote Similarity	NPD8127	Discontinued
0.6787	Remote Similarity	NPD7255	Clinical (unspecified phase)
0.6783	Remote Similarity	NPD5980	Discovery
0.6779	Remote Similarity	NPD4481	Phase 3
0.6762	Remote Similarity	NPD5844	Phase 1
0.6761	Remote Similarity	NPD2968	Approved
0.6761	Remote Similarity	NPD2971	Approved
0.6757	Remote Similarity	NPD7476	Discontinued
0.6744	Remote Similarity	NPD4084	Clinical (unspecified phase)
0.6738	Remote Similarity	NPD7907	Approved
0.6736	Remote Similarity	NPD7922	Phase 1
0.6726	Remote Similarity	NPD3448	Approved
0.6726	Remote Similarity	NPD2491	Approved
0.67	Remote Similarity	NPD6980	Clinical (unspecified phase)
0.6683	Remote Similarity	NPD6232	Discontinued
0.6682	Remote Similarity	NPD7546	Discontinued
0.6667	Remote Similarity	NPD7891	Discontinued
0.6667	Remote Similarity	NPD7473	Discontinued
0.6667	Remote Similarity	NPD3251	Approved
0.6653	Remote Similarity	NPD4846	Phase 2
0.6651	Remote Similarity	NPD5242	Approved
0.665	Remote Similarity	NPD6386	Approved
0.665	Remote Similarity	NPD6385	Approved
0.6638	Remote Similarity	NPD5676	Approved
0.6636	Remote Similarity	NPD7256	Discontinued
0.6635	Remote Similarity	NPD2821	Approved
0.662	Remote Similarity	NPD8055	Clinical (unspecified phase)
0.6618	Remote Similarity	NPD37	Approved
0.6606	Remote Similarity	NPD7235	Clinical (unspecified phase)
0.6604	Remote Similarity	NPD1221	Approved
0.6602	Remote Similarity	NPD4966	Approved
0.6602	Remote Similarity	NPD4965	Approved
0.6602	Remote Similarity	NPD4967	Phase 2
0.6594	Remote Similarity	NPD5914	Approved
0.6586	Remote Similarity	NPD8367	Approved
0.6581	Remote Similarity	NPD4665	Approved
0.6581	Remote Similarity	NPD4111	Phase 1
0.6579	Remote Similarity	NPD5950	Discontinued
0.6577	Remote Similarity	NPD2975	Approved
0.6577	Remote Similarity	NPD2973	Approved
0.6577	Remote Similarity	NPD2974	Approved
0.6575	Remote Similarity	NPD7708	Approved
0.6567	Remote Similarity	NPD8404	Phase 2
0.6565	Remote Similarity	NPD7783	Phase 2
0.6565	Remote Similarity	NPD7782	Clinical (unspecified phase)
0.6562	Remote Similarity	NPD4580	Approved
0.6553	Remote Similarity	NPD3437	Discontinued
0.6552	Remote Similarity	NPD7458	Discontinued
0.655	Remote Similarity	NPD6143	Clinical (unspecified phase)
0.654	Remote Similarity	NPD7278	Phase 2
0.654	Remote Similarity	NPD7279	Phase 2
0.6538	Remote Similarity	NPD6234	Discontinued
0.6537	Remote Similarity	NPD7827	Phase 1
0.6532	Remote Similarity	NPD7667	Clinical (unspecified phase)
0.6531	Remote Similarity	NPD2438	Suspended
0.6518	Remote Similarity	NPD7237	Clinical (unspecified phase)
0.6516	Remote Similarity	NPD6214	Clinical (unspecified phase)
0.6516	Remote Similarity	NPD6213	Phase 3
0.6516	Remote Similarity	NPD6212	Phase 3
0.6507	Remote Similarity	NPD5494	Approved
0.65	Remote Similarity	NPD2490	Approved
0.65	Remote Similarity	NPD2488	Approved
0.6498	Remote Similarity	NPD6997	Phase 2
0.6484	Remote Similarity	NPD3398	Discontinued
0.6482	Remote Similarity	NPD8492	Approved
0.6479	Remote Similarity	NPD7177	Discontinued
0.6478	Remote Similarity	NPD8151	Discontinued
0.6476	Remote Similarity	NPD7199	Phase 2
0.6476	Remote Similarity	NPD6457	Approved
0.6473	Remote Similarity	NPD7803	Approved
0.6471	Remote Similarity	NPD3912	Discontinued
0.6462	Remote Similarity	NPD1220	Phase 1
0.646	Remote Similarity	NPD2494	Approved
0.646	Remote Similarity	NPD2493	Approved
0.646	Remote Similarity	NPD3450	Approved
0.646	Remote Similarity	NPD3452	Approved
0.6456	Remote Similarity	NPD8155	Clinical (unspecified phase)
0.6453	Remote Similarity	NPD7047	Phase 3
0.6452	Remote Similarity	NPD8312	Approved
0.6452	Remote Similarity	NPD8313	Approved
0.6449	Remote Similarity	NPD7048	Phase 3
0.6447	Remote Similarity	NPD4582	Approved
0.6447	Remote Similarity	NPD4583	Approved
0.6443	Remote Similarity	NPD2979	Phase 3
0.6441	Remote Similarity	NPD5519	Discontinued
0.6435	Remote Similarity	NPD6559	Discontinued
0.6419	Remote Similarity	NPD7999	Approved
0.6416	Remote Similarity	NPD3290	Approved
0.6416	Remote Similarity	NPD3289	Phase 3
0.6415	Remote Similarity	NPD7184	Clinical (unspecified phase)
0.6414	Remote Similarity	NPD7858	Clinical (unspecified phase)
0.6408	Remote Similarity	NPD3752	Phase 2
0.6404	Remote Similarity	NPD4002	Approved
0.6404	Remote Similarity	NPD4004	Approved
0.6404	Remote Similarity	NPD7497	Discontinued
0.6402	Remote Similarity	NPD7893	Clinical (unspecified phase)
0.6402	Remote Similarity	NPD7228	Approved
0.64	Remote Similarity	NPD5071	Phase 2
0.6396	Remote Similarity	NPD7879	Clinical (unspecified phase)
0.6394	Remote Similarity	NPD5978	Approved
0.6394	Remote Similarity	NPD5616	Clinical (unspecified phase)
0.6394	Remote Similarity	NPD5977	Approved
0.6376	Remote Similarity	NPD7871	Phase 2
0.6376	Remote Similarity	NPD3534	Clinical (unspecified phase)
0.6376	Remote Similarity	NPD7870	Phase 2
0.6375	Remote Similarity	NPD4505	Phase 1
0.6372	Remote Similarity	NPD8285	Discontinued
0.6368	Remote Similarity	NPD3051	Approved
0.6364	Remote Similarity	NPD4868	Clinical (unspecified phase)
0.636	Remote Similarity	NPD956	Clinical (unspecified phase)
0.636	Remote Similarity	NPD7627	Approved
0.636	Remote Similarity	NPD7626	Approved
0.6359	Remote Similarity	NPD7038	Approved
0.6359	Remote Similarity	NPD7039	Approved
0.6359	Remote Similarity	NPD7685	Pre-registration
0.6357	Remote Similarity	NPD7862	Clinical (unspecified phase)
0.6344	Remote Similarity	NPD6780	Approved
0.6344	Remote Similarity	NPD6781	Approved
0.6344	Remote Similarity	NPD6782	Approved
0.6344	Remote Similarity	NPD6778	Approved
0.6344	Remote Similarity	NPD6777	Approved
0.6344	Remote Similarity	NPD6779	Approved
0.6344	Remote Similarity	NPD6776	Approved
0.6338	Remote Similarity	NPD2969	Approved
0.6338	Remote Similarity	NPD2970	Approved
0.6332	Remote Similarity	NPD7697	Approved
0.6332	Remote Similarity	NPD7696	Phase 3
0.6332	Remote Similarity	NPD7698	Approved
0.6329	Remote Similarity	NPD6873	Phase 2
0.6326	Remote Similarity	NPD3818	Discontinued
0.6326	Remote Similarity	NPD7799	Discontinued
0.6321	Remote Similarity	NPD2249	Approved
0.6321	Remote Similarity	NPD2247	Approved
0.632	Remote Similarity	NPD7583	Approved
0.6318	Remote Similarity	NPD7003	Approved
0.6316	Remote Similarity	NPD2358	Clinical (unspecified phase)
0.6314	Remote Similarity	NPD5025	Approved
0.6314	Remote Similarity	NPD8149	Discontinued
0.6314	Remote Similarity	NPD7475	Clinical (unspecified phase)
0.6313	Remote Similarity	NPD6496	Clinical (unspecified phase)
0.6309	Remote Similarity	NPD7875	Clinical (unspecified phase)
0.6309	Remote Similarity	NPD4997	Clinical (unspecified phase)
0.6309	Remote Similarity	NPD7874	Approved
0.6306	Remote Similarity	NPD5896	Clinical (unspecified phase)
0.63	Remote Similarity	NPD6874	Approved
0.6298	Remote Similarity	NPD3812	Clinical (unspecified phase)
0.6293	Remote Similarity	NPD7585	Approved
0.629	Remote Similarity	NPD8424	Clinical (unspecified phase)
0.629	Remote Similarity	NPD8434	Phase 2
0.629	Remote Similarity	NPD8150	Discontinued
0.6284	Remote Similarity	NPD7240	Approved
0.6279	Remote Similarity	NPD7955	Approved
0.6279	Remote Similarity	NPD7956	Approved
0.6273	Remote Similarity	NPD7090	Clinical (unspecified phase)
0.6271	Remote Similarity	NPD7930	Approved
0.6261	Remote Similarity	NPD7906	Approved
0.6261	Remote Similarity	NPD7435	Discontinued
0.6261	Remote Similarity	NPD1898	Discontinued
0.6261	Remote Similarity	NPD7693	Approved
0.625	Remote Similarity	NPD7584	Approved
0.625	Remote Similarity	NPD5805	Approved
0.625	Remote Similarity	NPD2672	Discontinued
0.624	Remote Similarity	NPD8461	Discontinued
0.6238	Remote Similarity	NPD4628	Phase 3
0.6234	Remote Similarity	NPD8320	Phase 1
0.6234	Remote Similarity	NPD8319	Approved
0.6233	Remote Similarity	NPD8435	Approved
0.6233	Remote Similarity	NPD8360	Approved
0.6233	Remote Similarity	NPD27	Approved
0.6233	Remote Similarity	NPD2489	Approved
0.6233	Remote Similarity	NPD8361	Approved
0.6232	Remote Similarity	NPD5811	Approved
0.623	Remote Similarity	NPD7654	Discontinued
0.6229	Remote Similarity	NPD7571	Clinical (unspecified phase)
0.6226	Remote Similarity	NPD919	Approved
0.6223	Remote Similarity	NPD7701	Phase 2
0.6221	Remote Similarity	NPD3965	Phase 1
0.6214	Remote Similarity	NPD7223	Discontinued
0.6214	Remote Similarity	NPD7224	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