NPASS Compound

Structure

NPC153651 OpenBabel07101718292D 44 47 0 0 1 0 0 0 0 0999 V2000 -11.2945 -2.3313 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2521 1.0163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5903 -0.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3222 0.5647 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7319 0.0259 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4360 -2.8442 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5626 -2.3572 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7042 -2.8701 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8308 -2.3831 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9723 -2.8960 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0989 -2.4090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2404 -2.9219 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3670 -2.4349 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5086 -2.9478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6352 -2.4609 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7767 -2.9738 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9033 -2.4868 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4921 0.7376 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7541 2.4778 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8584 -0.5129 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4412 3.1110 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0938 4.1369 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7169 1.0258 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3011 1.3254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7319 -0.0259 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4488 1.0517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4452 3.2006 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8884 1.4869 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6831 1.3254 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8884 -1.4869 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0150 0.9999 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9921 2.2764 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8584 0.5129 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9921 2.2764 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7468 0.9740 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1073 4.3007 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4338 2.0516 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7468 -0.9740 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5799 3.0854 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2232 2.9158 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3265 1.8813 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5903 0.5388 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0150 -0.9999 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 2 24 1 0 0 0 0 3 25 1 0 0 0 0 4 26 1 0 0 0 0 5 33 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 8 9 1 0 0 0 0 9 10 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 13 14 2 0 0 0 0 14 15 1 0 0 0 0 15 16 2 0 0 0 0 16 17 1 0 0 0 0 17 30 1 0 0 0 0 18 24 2 0 0 0 0 18 29 1 0 0 0 0 19 27 2 0 0 0 0 19 28 1 0 0 0 0 20 25 1 0 0 0 0 20 35 1 0 0 0 0 21 27 1 0 0 0 0 21 34 1 0 0 0 0 22 27 1 0 0 0 0 22 37 1 0 0 0 0 23 33 1 0 0 0 0 23 43 1 0 0 0 0 24 32 1 0 0 0 0 25 36 1 6 0 0 0 26 38 2 0 0 0 0 26 43 1 0 0 0 0 28 31 1 0 0 0 0 28 36 1 6 0 0 0 29 34 1 1 0 0 0 29 36 1 0 0 0 0 30 39 2 0 0 0 0 30 44 1 0 0 0 0 31 33 1 1 0 0 0 31 35 1 0 0 0 0 32 34 1 0 0 0 0 32 40 2 0 0 0 0 33 35 1 6 0 0 0 34 41 1 1 0 0 0 35 44 1 6 0 0 0 36 42 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	612.37
Volume:	648.853
LogP:	5.604
LogD:	3.997
LogS:	-4.608
# Rotatable Bonds:	16
TPSA:	130.36
# H-Bond Aceptor:	8
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.104
Synthetic Accessibility Score:	5.375
Fsp3:	0.694
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.786
MDCK Permeability:	2.810566729749553e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.052
20% Bioavailability (F20%):	0.428
30% Bioavailability (F30%):	0.461

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.964
Plasma Protein Binding (PPB):	93.35502624511719%
Volume Distribution (VD):	1.071
Pgp-substrate:	4.001691818237305%

ADMET: Metabolism

CYP1A2-inhibitor:	0.036
CYP1A2-substrate:	0.101
CYP2C19-inhibitor:	0.366
CYP2C19-substrate:	0.414
CYP2C9-inhibitor:	0.82
CYP2C9-substrate:	0.084
CYP2D6-inhibitor:	0.023
CYP2D6-substrate:	0.028
CYP3A4-inhibitor:	0.94
CYP3A4-substrate:	0.189

ADMET: Excretion

Clearance (CL):	2.056
Half-life (T1/2):	0.222

ADMET: Toxicity

hERG Blockers:	0.776
Human Hepatotoxicity (H-HT):	0.867
Drug-inuced Liver Injury (DILI):	0.173
AMES Toxicity:	0.088
Rat Oral Acute Toxicity:	0.96
Maximum Recommended Daily Dose:	0.994
Skin Sensitization:	0.965
Carcinogencity:	0.331
Eye Corrosion:	0.003
Eye Irritation:	0.014
Respiratory Toxicity:	0.959

Download Data

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

Natural Product: NPC153651

Natural Product ID:	NPC153651
*Common Name:**	Sapinsignoid D
IUPAC Name:	n.a.
Synonyms:	Sapinsignoid D
Standard InCHIKey:	UYPOIYOXALXFNN-UFANGNBOSA-N
Standard InCHI:	InChI=1S/C36H52O8/c1-6-7-8-9-10-11-12-13-14-15-16-17-30(39)44-35-20-25(3)36(42)28(31(35)33(35,5)23-43-26(4)38)19-27(22-37)21-34(41)29(36)18-24(2)32(34)40/h13-16,18-19,25,28-29,31,37,41-42H,6-12,17,20-23H2,1-5H3/b14-13+,16-15+/t25-,28+,29-,31-,33-,34-,35+,36-/m1/s1
SMILES:	CCCCCCCC/C=C/C=C/CC(=O)O[C@@]12C[C@@H](C)[C@]3([C@@H](C=C(C[C@]4([C@H]3C=C(C)C4=O)O)CO)[C@@H]1[C@@]2(C)COC(=O)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2042143
PubChem CID:	57408646
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002875] Tigliane and ingenane diterpenoids [CHEMONTID:0002906] Phorbol esters

*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
NPO158	Sapium insigne	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22409148]
NPO158	Sapium insigne	Species	Euphorbiaceae	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	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	IC50	=	900.0	nM	PMID[502747]

☑ 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 NPC153651 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	227
0.1-0.2	1257
0.2-0.3	4086
0.3-0.4	7535
0.4-0.5	14156
0.5-0.6	8750
0.6-0.7	5576
0.7-0.8	975
0.8-0.85	23
0.85-0.9	35
0.9-0.95	63
0.95-1	14

Similarity Score	Similarity Level	Natural Product ID
0.9817	High Similarity	NPC180640
0.9727	High Similarity	NPC19336
0.9727	High Similarity	NPC185876
0.9725	High Similarity	NPC472760
0.9533	High Similarity	NPC158523
0.9533	High Similarity	NPC475937
0.945	High Similarity	NPC474872
0.9439	High Similarity	NPC153036
0.9386	High Similarity	NPC145238
0.9358	High Similarity	NPC474937
0.9358	High Similarity	NPC71889
0.9286	High Similarity	NPC5991
0.9286	High Similarity	NPC471108
0.9286	High Similarity	NPC22628
0.9286	High Similarity	NPC275696
0.9286	High Similarity	NPC255081
0.9286	High Similarity	NPC5989
0.9266	High Similarity	NPC89227
0.9266	High Similarity	NPC265499
0.9266	High Similarity	NPC151216
0.9266	High Similarity	NPC101825
0.9266	High Similarity	NPC17138
0.9266	High Similarity	NPC221511
0.9266	High Similarity	NPC170212
0.9266	High Similarity	NPC215643
0.9266	High Similarity	NPC475391
0.9196	High Similarity	NPC472758
0.9196	High Similarity	NPC472397
0.9196	High Similarity	NPC171905
0.9196	High Similarity	NPC471125
0.9182	High Similarity	NPC477091
0.9174	High Similarity	NPC260786
0.9174	High Similarity	NPC96739
0.9174	High Similarity	NPC474871
0.9174	High Similarity	NPC174471
0.9123	High Similarity	NPC52839
0.9043	High Similarity	NPC257017
0.9043	High Similarity	NPC162009
0.9043	High Similarity	NPC19464
0.9035	High Similarity	NPC329080
0.9035	High Similarity	NPC472759
0.9035	High Similarity	NPC157252
0.9035	High Similarity	NPC471128
0.9035	High Similarity	NPC145182
0.9035	High Similarity	NPC471126
0.8957	High Similarity	NPC472401
0.8947	High Similarity	NPC156745
0.8947	High Similarity	NPC236918
0.8938	High Similarity	NPC156252
0.887	High Similarity	NPC475885
0.8839	High Similarity	NPC472757
0.8824	High Similarity	NPC236999
0.8803	High Similarity	NPC472399
0.8772	High Similarity	NPC10721
0.8761	High Similarity	NPC472400
0.8696	High Similarity	NPC146280
0.8696	High Similarity	NPC124676
0.8684	High Similarity	NPC234858
0.8684	High Similarity	NPC471127
0.8684	High Similarity	NPC154363
0.8583	High Similarity	NPC471940
0.85	High Similarity	NPC471939
0.85	High Similarity	NPC222307
0.8482	Intermediate Similarity	NPC163004
0.8417	Intermediate Similarity	NPC473919
0.8417	Intermediate Similarity	NPC473709
0.8361	Intermediate Similarity	NPC270109
0.8333	Intermediate Similarity	NPC473802
0.8205	Intermediate Similarity	NPC270958
0.819	Intermediate Similarity	NPC474271
0.8103	Intermediate Similarity	NPC71348
0.8095	Intermediate Similarity	NPC469674
0.807	Intermediate Similarity	NPC102843
0.8067	Intermediate Similarity	NPC118638
0.8051	Intermediate Similarity	NPC148458
0.8047	Intermediate Similarity	NPC243902
0.8034	Intermediate Similarity	NPC202889
0.8034	Intermediate Similarity	NPC469454
0.8034	Intermediate Similarity	NPC469463
0.8034	Intermediate Similarity	NPC469496
0.8031	Intermediate Similarity	NPC473548
0.8031	Intermediate Similarity	NPC471136
0.8031	Intermediate Similarity	NPC475500
0.8031	Intermediate Similarity	NPC100017
0.8031	Intermediate Similarity	NPC182266
0.8031	Intermediate Similarity	NPC223356
0.8031	Intermediate Similarity	NPC475154
0.8031	Intermediate Similarity	NPC471137
0.8	Intermediate Similarity	NPC472933
0.8	Intermediate Similarity	NPC472667
0.8	Intermediate Similarity	NPC221414
0.7983	Intermediate Similarity	NPC471854
0.7966	Intermediate Similarity	NPC67290
0.7966	Intermediate Similarity	NPC138303
0.7966	Intermediate Similarity	NPC133677
0.7965	Intermediate Similarity	NPC118911
0.7951	Intermediate Similarity	NPC222688
0.7949	Intermediate Similarity	NPC76550
0.7949	Intermediate Similarity	NPC170487
0.7949	Intermediate Similarity	NPC123855
0.7928	Intermediate Similarity	NPC470074
0.7917	Intermediate Similarity	NPC21326
0.7907	Intermediate Similarity	NPC68282
0.7899	Intermediate Similarity	NPC179626
0.7881	Intermediate Similarity	NPC46269
0.7881	Intermediate Similarity	NPC472926
0.7881	Intermediate Similarity	NPC106395
0.7881	Intermediate Similarity	NPC25909
0.7874	Intermediate Similarity	NPC473485
0.7874	Intermediate Similarity	NPC180902
0.7874	Intermediate Similarity	NPC475139
0.7874	Intermediate Similarity	NPC474508
0.7863	Intermediate Similarity	NPC179798
0.7863	Intermediate Similarity	NPC304180
0.7863	Intermediate Similarity	NPC214797
0.7863	Intermediate Similarity	NPC231589
0.7863	Intermediate Similarity	NPC118860
0.7857	Intermediate Similarity	NPC115862
0.7857	Intermediate Similarity	NPC115899
0.7845	Intermediate Similarity	NPC258543
0.7845	Intermediate Similarity	NPC273433
0.7845	Intermediate Similarity	NPC241927
0.7833	Intermediate Similarity	NPC472934
0.7833	Intermediate Similarity	NPC472927
0.7833	Intermediate Similarity	NPC239273
0.7812	Intermediate Similarity	NPC469673
0.7798	Intermediate Similarity	NPC217624
0.7798	Intermediate Similarity	NPC181393
0.7797	Intermediate Similarity	NPC475524
0.7797	Intermediate Similarity	NPC100267
0.7797	Intermediate Similarity	NPC152117
0.7797	Intermediate Similarity	NPC234042
0.7797	Intermediate Similarity	NPC138757
0.7795	Intermediate Similarity	NPC475314
0.7795	Intermediate Similarity	NPC477189
0.7795	Intermediate Similarity	NPC220757
0.7795	Intermediate Similarity	NPC251564
0.7795	Intermediate Similarity	NPC475606
0.7795	Intermediate Similarity	NPC196921
0.7788	Intermediate Similarity	NPC478156
0.7787	Intermediate Similarity	NPC143755
0.7787	Intermediate Similarity	NPC41123
0.7787	Intermediate Similarity	NPC114939
0.7787	Intermediate Similarity	NPC145074
0.7778	Intermediate Similarity	NPC5103
0.7778	Intermediate Similarity	NPC238850
0.7769	Intermediate Similarity	NPC257457
0.7769	Intermediate Similarity	NPC311554
0.7768	Intermediate Similarity	NPC266955
0.776	Intermediate Similarity	NPC63186
0.776	Intermediate Similarity	NPC15095
0.7759	Intermediate Similarity	NPC476479
0.7759	Intermediate Similarity	NPC322903
0.7752	Intermediate Similarity	NPC476823
0.7739	Intermediate Similarity	NPC60315
0.7734	Intermediate Similarity	NPC90814
0.7734	Intermediate Similarity	NPC189393
0.7734	Intermediate Similarity	NPC34963
0.7731	Intermediate Similarity	NPC56448
0.7731	Intermediate Similarity	NPC962
0.7724	Intermediate Similarity	NPC310511
0.7719	Intermediate Similarity	NPC475623
0.7719	Intermediate Similarity	NPC475334
0.7719	Intermediate Similarity	NPC473694
0.7719	Intermediate Similarity	NPC72151
0.7719	Intermediate Similarity	NPC478057
0.7717	Intermediate Similarity	NPC162495
0.7717	Intermediate Similarity	NPC470880
0.7717	Intermediate Similarity	NPC35109
0.7712	Intermediate Similarity	NPC473921
0.7712	Intermediate Similarity	NPC475668
0.7712	Intermediate Similarity	NPC475480
0.7705	Intermediate Similarity	NPC470186
0.7699	Intermediate Similarity	NPC146822
0.7699	Intermediate Similarity	NPC476223
0.7699	Intermediate Similarity	NPC476240
0.7699	Intermediate Similarity	NPC224720
0.7699	Intermediate Similarity	NPC118174
0.7698	Intermediate Similarity	NPC470882
0.7698	Intermediate Similarity	NPC473265
0.7698	Intermediate Similarity	NPC473253
0.7692	Intermediate Similarity	NPC304495
0.7692	Intermediate Similarity	NPC137911
0.7692	Intermediate Similarity	NPC228477
0.7686	Intermediate Similarity	NPC474518
0.7686	Intermediate Similarity	NPC23046
0.7674	Intermediate Similarity	NPC476111
0.7674	Intermediate Similarity	NPC58029
0.7672	Intermediate Similarity	NPC473284
0.7669	Intermediate Similarity	NPC25887
0.7661	Intermediate Similarity	NPC23786
0.7661	Intermediate Similarity	NPC470265
0.7656	Intermediate Similarity	NPC279478
0.7656	Intermediate Similarity	NPC241935
0.7652	Intermediate Similarity	NPC201144
0.7652	Intermediate Similarity	NPC103298
0.7652	Intermediate Similarity	NPC181104
0.7652	Intermediate Similarity	NPC288502
0.7652	Intermediate Similarity	NPC121518
0.7652	Intermediate Similarity	NPC475331

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 NPC153651 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	196
0.1-0.2	1575
0.2-0.3	3594
0.3-0.4	2415
0.4-0.5	913
0.5-0.6	278
0.6-0.7	167
0.7-0.8	12
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
0.7712	Intermediate Similarity	NPD6649	Approved
0.7712	Intermediate Similarity	NPD6650	Approved
0.7647	Intermediate Similarity	NPD8297	Approved
0.7627	Intermediate Similarity	NPD6371	Approved
0.7607	Intermediate Similarity	NPD6899	Approved
0.7607	Intermediate Similarity	NPD6881	Approved
0.7563	Intermediate Similarity	NPD8130	Phase 1
0.7542	Intermediate Similarity	NPD6372	Approved
0.7542	Intermediate Similarity	NPD6373	Approved
0.7521	Intermediate Similarity	NPD5697	Approved
0.75	Intermediate Similarity	NPD6882	Approved
0.7479	Intermediate Similarity	NPD6883	Approved
0.7479	Intermediate Similarity	NPD7290	Approved
0.7479	Intermediate Similarity	NPD7102	Approved
0.7436	Intermediate Similarity	NPD6402	Approved
0.7436	Intermediate Similarity	NPD5739	Approved
0.7436	Intermediate Similarity	NPD6675	Approved
0.7436	Intermediate Similarity	NPD7128	Approved
0.7417	Intermediate Similarity	NPD6869	Approved
0.7417	Intermediate Similarity	NPD6617	Approved
0.7417	Intermediate Similarity	NPD6847	Approved
0.7395	Intermediate Similarity	NPD6012	Approved
0.7395	Intermediate Similarity	NPD6014	Approved
0.7395	Intermediate Similarity	NPD6013	Approved
0.736	Intermediate Similarity	NPD6319	Approved
0.7328	Intermediate Similarity	NPD5211	Phase 2
0.7323	Intermediate Similarity	NPD7604	Phase 2
0.7311	Intermediate Similarity	NPD7320	Approved
0.7311	Intermediate Similarity	NPD6011	Approved
0.7295	Intermediate Similarity	NPD4632	Approved
0.7258	Intermediate Similarity	NPD7115	Discovery
0.7227	Intermediate Similarity	NPD5701	Approved
0.7222	Intermediate Similarity	NPD1696	Phase 3
0.7203	Intermediate Similarity	NPD5141	Approved
0.7155	Intermediate Similarity	NPD5285	Approved
0.7155	Intermediate Similarity	NPD7639	Approved
0.7155	Intermediate Similarity	NPD7640	Approved
0.7155	Intermediate Similarity	NPD5286	Approved
0.7155	Intermediate Similarity	NPD4696	Approved
0.7143	Intermediate Similarity	NPD6008	Approved
0.7132	Intermediate Similarity	NPD7492	Approved
0.713	Intermediate Similarity	NPD6084	Phase 2
0.713	Intermediate Similarity	NPD6083	Phase 2
0.712	Intermediate Similarity	NPD6009	Approved
0.7099	Intermediate Similarity	NPD7736	Approved
0.7087	Intermediate Similarity	NPD6054	Approved
0.7083	Intermediate Similarity	NPD7899	Clinical (unspecified phase)
0.7077	Intermediate Similarity	NPD6616	Approved
0.7069	Intermediate Similarity	NPD7638	Approved
0.7034	Intermediate Similarity	NPD5224	Approved
0.7034	Intermediate Similarity	NPD5225	Approved
0.7034	Intermediate Similarity	NPD5226	Approved
0.7034	Intermediate Similarity	NPD4633	Approved
0.7031	Intermediate Similarity	NPD5983	Phase 2
0.7023	Intermediate Similarity	NPD7078	Approved
0.7009	Intermediate Similarity	NPD6648	Approved
0.7008	Intermediate Similarity	NPD7101	Approved
0.7008	Intermediate Similarity	NPD7100	Approved
0.6992	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6983	Remote Similarity	NPD4755	Approved
0.6977	Remote Similarity	NPD6370	Approved
0.6975	Remote Similarity	NPD5174	Approved
0.6975	Remote Similarity	NPD5175	Approved
0.6957	Remote Similarity	NPD5695	Phase 3
0.6949	Remote Similarity	NPD5344	Discontinued
0.6949	Remote Similarity	NPD5223	Approved
0.6947	Remote Similarity	NPD6336	Discontinued
0.693	Remote Similarity	NPD5779	Approved
0.693	Remote Similarity	NPD5778	Approved
0.6929	Remote Similarity	NPD6335	Approved
0.6923	Remote Similarity	NPD5696	Approved
0.6911	Remote Similarity	NPD4634	Approved
0.6911	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6905	Remote Similarity	NPD6274	Approved
0.6899	Remote Similarity	NPD6016	Approved
0.6899	Remote Similarity	NPD6015	Approved
0.6894	Remote Similarity	NPD8293	Discontinued
0.6885	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6885	Remote Similarity	NPD4729	Approved
0.6885	Remote Similarity	NPD4730	Approved
0.687	Remote Similarity	NPD5282	Discontinued
0.6864	Remote Similarity	NPD4700	Approved
0.685	Remote Similarity	NPD6317	Approved
0.6846	Remote Similarity	NPD5988	Approved
0.6842	Remote Similarity	NPD5284	Approved
0.6842	Remote Similarity	NPD7983	Approved
0.6842	Remote Similarity	NPD5281	Approved
0.6838	Remote Similarity	NPD7902	Approved
0.6829	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6822	Remote Similarity	NPD6059	Approved
0.6818	Remote Similarity	NPD7507	Approved
0.681	Remote Similarity	NPD5210	Approved
0.681	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.681	Remote Similarity	NPD4629	Approved
0.681	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.68	Remote Similarity	NPD6053	Discontinued
0.6797	Remote Similarity	NPD6313	Approved
0.6797	Remote Similarity	NPD6314	Approved
0.6794	Remote Similarity	NPD8328	Phase 3
0.6783	Remote Similarity	NPD6399	Phase 3
0.678	Remote Similarity	NPD4225	Approved
0.6774	Remote Similarity	NPD5250	Approved
0.6774	Remote Similarity	NPD5251	Approved
0.6774	Remote Similarity	NPD5247	Approved
0.6774	Remote Similarity	NPD5248	Approved
0.6774	Remote Similarity	NPD5249	Phase 3
0.6769	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6754	Remote Similarity	NPD7838	Discovery
0.6752	Remote Similarity	NPD5222	Approved
0.6752	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6752	Remote Similarity	NPD5221	Approved
0.6748	Remote Similarity	NPD6686	Approved
0.6724	Remote Similarity	NPD7748	Approved
0.6721	Remote Similarity	NPD4767	Approved
0.6721	Remote Similarity	NPD4768	Approved
0.6696	Remote Similarity	NPD6050	Approved
0.6696	Remote Similarity	NPD5694	Approved
0.6696	Remote Similarity	NPD7637	Suspended
0.6696	Remote Similarity	NPD6079	Approved
0.6695	Remote Similarity	NPD5173	Approved
0.6691	Remote Similarity	NPD7260	Phase 2
0.6667	Remote Similarity	NPD4753	Phase 2
0.6667	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD7319	Approved
0.6641	Remote Similarity	NPD8515	Approved
0.6641	Remote Similarity	NPD6908	Approved
0.6641	Remote Similarity	NPD6909	Approved
0.6641	Remote Similarity	NPD8516	Approved
0.6641	Remote Similarity	NPD7503	Approved
0.6641	Remote Similarity	NPD8517	Approved
0.6641	Remote Similarity	NPD8513	Phase 3
0.6641	Remote Similarity	NPD6868	Approved
0.6639	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6613	Remote Similarity	NPD5128	Approved
0.6612	Remote Similarity	NPD7632	Discontinued
0.661	Remote Similarity	NPD4697	Phase 3
0.6609	Remote Similarity	NPD6698	Approved
0.6609	Remote Similarity	NPD5785	Approved
0.6609	Remote Similarity	NPD5692	Phase 3
0.6609	Remote Similarity	NPD46	Approved
0.6587	Remote Similarity	NPD5217	Approved
0.6587	Remote Similarity	NPD5216	Approved
0.6587	Remote Similarity	NPD5215	Approved
0.6581	Remote Similarity	NPD7900	Approved
0.6581	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6579	Remote Similarity	NPD6672	Approved
0.6579	Remote Similarity	NPD5737	Approved
0.6557	Remote Similarity	NPD4754	Approved
0.6552	Remote Similarity	NPD7515	Phase 2
0.6552	Remote Similarity	NPD6411	Approved
0.6538	Remote Similarity	NPD7328	Approved
0.6538	Remote Similarity	NPD7327	Approved
0.6522	Remote Similarity	NPD6673	Approved
0.6522	Remote Similarity	NPD5328	Approved
0.6522	Remote Similarity	NPD6904	Approved
0.6522	Remote Similarity	NPD6080	Approved
0.6522	Remote Similarity	NPD1695	Approved
0.6515	Remote Similarity	NPD8033	Approved
0.6508	Remote Similarity	NPD5169	Approved
0.6508	Remote Similarity	NPD5134	Clinical (unspecified phase)
0.6508	Remote Similarity	NPD5135	Approved
0.6496	Remote Similarity	NPD4202	Approved
0.6491	Remote Similarity	NPD3573	Approved
0.6489	Remote Similarity	NPD7516	Approved
0.6471	Remote Similarity	NPD7839	Suspended
0.6466	Remote Similarity	NPD5207	Approved
0.6462	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.646	Remote Similarity	NPD1694	Approved
0.646	Remote Similarity	NPD5363	Approved
0.6457	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6457	Remote Similarity	NPD5127	Approved
0.6441	Remote Similarity	NPD6001	Approved
0.6439	Remote Similarity	NPD8294	Approved
0.6439	Remote Similarity	NPD8377	Approved
0.6429	Remote Similarity	NPD5362	Discontinued
0.6429	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD7154	Phase 3
0.6417	Remote Similarity	NPD5959	Approved
0.641	Remote Similarity	NPD8035	Phase 2
0.641	Remote Similarity	NPD5693	Phase 1
0.641	Remote Similarity	NPD8034	Phase 2
0.6404	Remote Similarity	NPD5280	Approved
0.6404	Remote Similarity	NPD5279	Phase 3
0.6404	Remote Similarity	NPD4694	Approved
0.6404	Remote Similarity	NPD3618	Phase 1
0.6404	Remote Similarity	NPD5690	Phase 2
0.64	Remote Similarity	NPD6412	Phase 2
0.6397	Remote Similarity	NPD8074	Phase 3
0.6391	Remote Similarity	NPD6921	Approved
0.6391	Remote Similarity	NPD8335	Approved
0.6391	Remote Similarity	NPD8296	Approved
0.6391	Remote Similarity	NPD8378	Approved
0.6391	Remote Similarity	NPD8380	Approved
0.6391	Remote Similarity	NPD8379	Approved
0.6379	Remote Similarity	NPD6101	Approved
0.6379	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6379	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.6372	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6357	Remote Similarity	NPD8133	Approved
0.635	Remote Similarity	NPD6033	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